BIOLOGY 

LIBRARY 

G 


MODERN  PROBLEMS  OF  BIOLOGY 


MI  N  OT 


BY  THE  SAME  AUTHOR 

Embryology.  A  Laboratory  Text-book 
of  Embryology.  By  CHARLES  S.  MINOT, 
S.D.,  LL.D.,  Professor  of  Comparative  An- 
atomy, Harvard  University  Medical  School. 
Second  Edition,  Revised.  With  262  Illus. 
xiix402  pages.  Cloth,  3.50. 

"Professor  Minot  is  to  be  congratulated  most 
warmly  on  the  success,  efficiency,  thoroughness, 
and  stimulating  character  of  his  work." — The  Lan- 
cet, London. 

"The  book  is  well  written  and  well  printed. 
The  illustrations  are  numerous  and  well  executed." 
— New  York  Medical  Journal. 

P.  BLAKISTON'S  SON  &  CO. 

PHILADELPHIA 


MODERN  PROBLEMS  OF  BIOLOGY 


LECTURES  DELIVERED  AT  THE  UNIVERSITY  OF  JENA, 
DECEMBER,  1912 


BY 

CHARLES    SEDGWICK   MINOT 

LL.  D.,  YALE  TORONTO  AND  ST.  ANDREWS;  D.  SC.,  OXFORD;  DIRECTOR 
OF  THE  ANATOMICAL  LABORATORIES,  HARVARD  MEDICAL 
SCHOOL;  EXCHANGE  PROFESSOR.  AT  THE  UNIVER- 
SITIES OF  BERLIN  AND  JENA,    IQI2-I3. 


WITH  FIFTY-THREE  ILLUSTRATIONS 


PHILADELPHIA 
P.   BLAKISTON'S   SON   &   CO. 

1012   WALNUT   STREET 
1913 


BIOLOGY 

LIBRARY 

G 


COPYRIGHT,  1913,  BY  P.  BLAKISTON'S  SON  &  Co. 


THE. MAPLE. PRESS. YORK. PA 


TO  THE 

UNIVERSITY  OF  JENA 


281435 


PREFACE 


His  Royal  Highness,  the  Grand-Duke  of  Saxe- Weimar,  the 
Rector  Magnificentissimus  of  the  University,  has  graciously 
pleased,  after  Professor  Eucken  of  Jena  had  been  called  to 
Harvard  University  as  Exchange  Professor,  to  express  the 
wish  that  the  Harvard  Exchange  Professor  at  Berlin  this  year 
should  lecture  also  in  Jena.  This  wish  was  communicated  to 
Harvard  University  by  the  Prussian  Ministry  of  Education. 
After  further  correspondence  the  formal  invitation  was  sent 
me  to  deliver  in  Jena  the  six  lectures  which  appear  in  printed 
form  in  the  following  pages. 

It  is  always  a  difficult  problem  to  so  present  new  biological 
discoveries  that  they  will  be  comprehensible  to  a  mixed  public, 
and  yet  lose  nothing  of  their  scientific  value.  The  reader 
therefore  is  requested  to  exercise  a  lenient  judgment,  when  he 
finds  that  the  performance  leaves  much  to  be  desired.  It 
seemed  desirable  to  consider  the  first  lecture  as  an  introduc- 
tion which  might  render  it  easier  for  non-biologists  to  under- 
stand the  following  lectures.  The  researches  quoted  are 
chiefly  American.  This  plan  was  adopted  partly  because  the 
author  was  the  American  Exchange  Professor  and  partly  be- 
cause he  was  informed  that  his  audience  in  Jena  would  like 
to  hear  especially  about  American  discoveries.  In  the  short 
time  at  command  it  was  impossible  to  present  the  evidence  for 
all  that  was  said,  and  the  reader  must  be  begged  to  pardon  the 
author  if  many  assertions  sound  like  obiter  dicta. 

vii 


Vlll 


To  their  Royal  Highnesses,  the  Grand-duke  and  the  Grand- 
duchess  of  Saxony,  the  author  expresses  his  thanks  for  their 
interest  and  for  the  great  honor  of  their  presence  at  one  of  the 
lectures.  He  has  pleasure  in  thanking  also  their  Excellencies, 
the  Ministers  of  Education  of  Saxe-Weimar-Eisenach, 
Altenburg  and  Meiningen,  his  Magnificency  the  Prorektor, 
the  Curator  of  the  University  and  his  Colleagues  for  their 
encouragement  and  hospitality,  by  which  the  visit  to  Jena  was 
made  very  delightful. 

The  lectures  were  written  and  have  already  been  published 
in  German  by  Gustav  Fischer  in  Jena.  Professor  von  Bar- 
deleben  had  the  great  kindness  to  revise  the  original  manu- 
script. The  translation  has  been  prepared  by  the  author  and 
follows  the  original  closely,  though  now  and  then  a  phrase 
has  been  rendered  freely. 

CHARLES  S.  MINOT. 

BOSTON. 


CONTENTS 

PAGE 

PREFACE vii 

1.  THE  NEW  CELL  DOCTRINE i 

2.  CYTOMORPHOSIS 24 

3.  THE  DOCTRINE  OF  IMMORTALITY 43 

4.  THE  DEVELOPMENT  OF  DEATH .    .    .  59 

5.  THE  DETERMINATION  OF  SEX 82 

6.  THE  NOTION  OF  LIFE 


IX 


PROBLEMS  IN  BIOLOGY 


THE  NEW  CELL  DOCTRINE 

Your  Magnificence! 
Gentlemen ! 

To  his  Royal  Highness,  the  Grand  Duke  of  Saxe- Weimar, 
I  wish  to  express  with  the  highest  respect  my  sincere  thanks 
for  the  interest  which  his  Royal  Highness  has  shown  in  the 
exchange  of  professors  with  America.  It  is  a  great  honor  to 
be  the  first  Harvard  professor  to  come  to  you,  as  the  official 
representative  of  the  American  academical  world.  The 
University  of  Jena  is  as  famous  and  as  highly  esteemed  in 
America  as  in  Germany.  When  I  consider  the  reputation  of 
the  Jena  professors  I  cannot  venture  to  hope  that  the  lectures 
I  am  to  deliver  will  attain  that  degree  of  perfection  to  which 
you  are  accustomed.  Therefore  I  request  you  to  consider 
my  lectures  as  an  expression  of  my  sense  of  obligation.  Not 
merely  Harvard  University,  but  the  whole  United  States  are 
grateful  to  you  that  you  have  permitted  Professor  Eucken 
to  come  to  us  as  exchange  professor.  I  owe  your  Ministry  of 
Education  special  thanks  for  the  invitation  sent  me  to  appear 
here  as  the  guest  of  your  University. 

It  is  always  a  difficult  task  so  to  present  scientific  conclu- 
sions that  they  shall  be  comprehensible  to  the  public  and,  at 
the  same  time,  keep  their  precision  and  their  scientific  value; 
but  when  a  branch  of  science  has  progressed  so  far  that 

i 


2  THE    NEW    CELL   DOCTRINE 

conclusions  of  wide  bearing  can  be  drawn,  it  becomes  desirable 
to  communicate  the  results  to  wider  circles.  The  new 
achievements  of  biology  are  significant  and  claim  the  interest 
of  all  thinkers,  and  therefore  I  have  decided  to  attempt  to 
make  clear  to  you  some  of  our  fundamental  conclusions.  My 
fellow  biologists  are  requested  to  excuse  the  mention  of  much 
already  known  to  them. 

The  general  conclusions  of  biology  are  formed  slowly. 
The  phenomena  of  life  are  so  complicated  that  they  can  be 
analyzed  only  by  the  most  many-sided  investigations.  If 
one  wishes  completely  to  master  the  science  one  would  have  to 
be  not  only  a  biologist  in  the  stricter  sense,  but  also  a  chemist, 
a  physicist  and  a  geologist.  It  has  become  impossible  for  a 
single  investigator  of  our  time  to  acquire  special  knowledge 
in  the  whole  field  of  biology,  and  you  will  certainly  not  expect 
from  me  that  I  attempt  to  make  clear  to  you  all  the  funda- 
mental conclusions  of  modern  biology.  Indeed  for  this,  the 
time  at  our  disposal  would  not  suffice.  Therefore  I  shall 
permit  myself  to  treat  only  such  questions  as  I  have  found 
occasion  to  consider  often  in  the  course  of  my  special  work. 
We  may  arrange  the  subjects  to  be  discussed  in  the  following 
order : 

1.  The  New  Cell  Doctrine. 

2.  Cytomorphosis. 

3.  The  Doctrine  of  Immortality. 

4.  The  Development  of  Death. 

5.  The  Determination  of  Sex. 

6.  The  Notion  of  Life. 

You  all  know  something  of  cells,  which  have  been  described 
often  as  the  units  of  life.  They  are  small  masses  of  living  sub- 
stance, in  each  of  which  lies  a  smaller  body,  which  is  desig- 


THE    NEW    CELL   DOCTRINE 


nated  as  nucleus.  The  living  sub- 
stance is  commonly  termed  proto- 
plasm. Unfortunately  with  the 
progress  of  investigation  we  have 
become  more  and  more  uncertain 
what  we  can  properly  designate  as 
protoplasm.  The  nucleus  is  also  a 
living  substance,  but  it  is  commonly 
not  reckoned  as  protoplasm.  Many 
authors  apply  the  term  protoplasm 
to  the  body  of  the  cell,  which  often 
has  a  very  complicated  structure. 
Thus  we  see  spaces  which  we  name 
vacuoles,  and  which  contain  only 
fluid.  Such  a  fluid  is  usually  not 
considered  part  of  the  protoplasm. 
More  frequently  we  find  special  en- 
closures, granules,  etc.,  which  reveal 


FIG.  i. — Two  blood  cells  from  an  embryo  duck. 
The  protoplasm  has  a  uniform  constitution  and 
contains  the  centrosome.  In  the  rounded  nucleus 
the  material  is  irregularly  distributed  and  forms 
a  larger  mass  of  chromatine.  The  cells  have  been 
artificially  colored. — After  M,  Heidenhain. 


FIG.  2. — Two  plant  cells 
from  the  vegetative  point  of 
a  Phanerogam,  a,  younger; 
6,  older  stage;  k,  nucleus;  v, 
sap  space;  cy,  protoplasm. — • 
After  Strassburger. 


an  entirely  different  constitution  from  the  rest  of  the  mass, 
which  one  is  inclined  to  name  protoplasm  in   the   stricter 


4  THE    NEW   CELL   DOCTRINE 

sense.  A  further  difficulty  arises  from  the  observation  that 
in  the  nucleus  also  a  substance  can  be  found  with  peculiari- 
ties like  the  protoplasm.  Thus  it  happens  that  with  the 
enlargement  of  our  knowledge  we  have  become  more  and 
more  uncertain  what  we  can  properly  designate  with  this 
word  "protoplasm."  It  corresponds  better  to  the  present 
condition  of  science  if  we  say  that  a  cell  consists  of  nucleus 
and  a  cell  body,  because  we  thus  restate  clearly  our  direct 
observation.  Nevertheless  a  biologist  would  hardly  like  to 
lay  aside  the  word  protoplasm,  in  part  because  it  has  such  a 
great  historic  significance. 

As  is  known,  cells  were  discovered  by  the  botanists,  and 
first  by  the  Englishman  Hook,  and  they  received  from  botan- 
ists the  name  cell,  which  is  completely  suitable  for  the  form 
first  observed,  for  in  many  plants  one  sees  the  cells  as  small 
spaces,  which  are  separated  from  one  another  by  partitions. 
These  spaces  were  designated  simply  as  cells.  Later  it  was  rec- 
ognized that  the  essential  thing  was  not  the  arrangement  of 
the  partitions,  but  the  content  of  each  cell.  This  content  is 
protoplasm  mixed  with  water  and  containing  a  nucleus.  Two 
eminent  German  investigators  have  furnished  us  with  a 
completely  new  conception  of  tne  cell.  Wilhelm  Kiihne  and 
Max  Schulze  have  proven  that  the  partitions  are  unessential 
and  that  we  may  have  a  complete  cell  without  them.  Thus  a 
new  conception  arose,  namely,  that  a  cell  consists  of  proto- 
plasm and  nucleus.  The  great  English  biologist,  Huxley,  who 
appreciated  the  importance  of  the  new  views  of  Kiihne  and 
Schulze,  has  presented  them  in  a  lecture  to  which  he  gave  the 
title,  "The  Physical  Basis  of  Life."  Huxley's  presentation  is 
so  clear  and  comprehensible  that  his  readers  cannot  fail  to  ap- 
preciate the  full  significance  of  the  views  presented.  Huxley's 
lecture  occasioned  great  excitement  among  thinkers  in  Eng- 


THE    NEW   CELL   DOCTRINE  5 

land  and  America,  and  also  on  the  European  Continent. 
Everybody  discussed  at  that  time  the  question  whether  proto- 
plasm was  really  the  physical  basis  of  life  or  not.  The  solution 
of  this  problem  we  have  not  fully  reached  even  yet.  The  de- 
scription of  the  cell  which  we  owe  to  Max  Schulze  dominates 
everywhere  and  yet  with  the  progress  of  science  it  has  be- 
come insufficient. 

The  size  of  the  cell  is  of  the  greatest  significance  to  biologists. 
Cells  for  the  most  part  are  rather  small,  and  the  size  is  ex- 
tremely variable.  The  cells  of  the  human  body,  according  to 
an  estimate  I  have  made,  have  an  average  diameter  of  perhaps 
0.014  mm.  Variations,  however,  are  considerable;  some  cells, 
like  the  blood-corpuscles,  are  very  small;  certain  nerve  cells, 
on  the  other  hand,  attain  a  considerable  size.  The  largest 
cells  of  all,  known  to  us  at  present,  are  eggs.  Those  of  certain 
animals  appear  as  true  giants  in  comparison  with  other  cells. 
The  largest  eggs  occur  in  birds.  The  entire  yolk  of  the  bird's 
egg  corresponds  to  but  a  single  cell.  The  albumen  which 
surrounds  the  yolk  and  the  shell  do  not  belong  to  this  cell,  but 
are  simply  layers  which  are  added  by  the  oviduct  to  the  egg 
proper,  and  which  are  secretions  of  the  glands  of  the  oviduct. 
Of  all  the  animals  now  living  the  ostrich  has  the  largest  egg 
and  the  yolk  of  the  ostrich  egg  is  certainly  the  largest  living 
cell  known  to  us.  These  enormously  enlarged  eggs  might  be 
described  as  the  monsters  of  the  cellular  world.  They  are  ex- 
ceptions. By  far  the  majority  of  cells  are  of  such  dimensions 
that  they  are  visible  with  the  microscope  alone.  The  smallest 
organisms  which  we  know  are  the  vegetable  germs,  which  may 
have  a  diameter  of  not  more  than  one-tenth  of  a  millimeter. 
As  is  well  known  to  all,  certain  of  these  smallest  organisms 
cause  diseases  which  may  be  extremely  dangerous  to  man. 
The  investigators  of  infectious  diseases  have  made  the  inter- 


THF   NEW   CELL   DOCTRINE 


esting  discovery  that  there  are  disease  causers  which  are  in- 
visible even  with  the  microscope.     In  recent  years  we  hear 
more  and  more  of  the  so-called  invisible  organisms.     In  re- 
gard to  this  we  must  express  our  opinion  with  reservation,  for 
it  is  by  no  means  demonstrated  that  we  have  to  deal  in  this 
case  with  actually  living  organisms.    It  is  possible  that  we  have 
to  do  only  with  chemical  ferments.     We  have  not  time,  how- 
ever, to  enter  upon  this  discussion.    For 
the  present  at  least  we  must  hold  to 
the  opinion  that  vital  phenomena  can 
appear  only  when  the  amount  of  living 
substance  is  so  great  that  it  can  be 
seen  with  the  microscope.      In  other 
words,  the  minimum  quantity  of  chem- 
ical substance  which  can  serve  as  the 
basis  of  life  is  many  times  greater  than 
the  minimum  quantity   of    substance 
which  suffices  for  a  chemical  reaction. 
Here  we  encounter  a  fundamental  char- 
acteristic of  life      To  permit  the  activ- 
ities which  are  characteristic  for  life  to 
go  on  we  must  bring  together  many  sub- 
stances which   stand  in   very   special 
relations  to  one  another.     Hence  the 
assertion  that  life  is  only  possible  when  these  conditions  are 
fulfilled,  and  this  requires  that  the  total  amount  should  be 
so  much  that  we  can  see  it  with  the  microscope. 

Cells  have  been  considered  for  a  long  time  as  independent 
bodies.  Quite  slowly  this  view  has  been  changing.  Many 
years  ago  botanists  made  the  observation  that  vegetable 
cells  may  be  united  by  fine  threads  of  living  substance. 
Similar  relations  have  been  observed  in  animals.  In  the  sev- 


FIG.  3. — Drawing  to 
show  the  size  of  bacteria. 
Magnification  1000  (i  mm. 
of  the  picture  =0.001). 
Ay  smallest  bacilli  (influ- 
enza); 5,  streptococcus 
gracilis  (round);  C,  largest 
cocci;  D,  pus  cocci;  E,  ba- 
cillus megatherium;  F,  red 
blood  corpuscle;  G,  splenic 
fever  bacillus. — After  H. 
Jaeger. 


THE    NEW   CELL   DOCTRINE 


enties  of  the  last 
century  J.  Heitz- 
mann,  a  Viennese 
physician  who  had 
emigrated  to  New 
York,  affirmed  that 
cells  are  not  defi- 
nitely separated 
from  one  another. 
He  advanced  the 
statement  that 
protoplasm  is  con- 
tinuous and  has 
scattered  nuclei. 
The  opinions  ex- 
pressed by  Heitz- 
mann1  remained  in 
their  time  almost 
without  notice. 
Very  gradually  his 
view  met  with 
wider  acceptance. 
The  botanist  Sachs 
has  contributed 
much  to  develop 
our  interpretation. 
For  the  zoologists 
the  writings  of  the 
American  Whit- 
man2 have  been  of 
the  greatest  im- 
portance. Whit- 


17 

«    d 
•+*    3 

O     bO 


11 


8  THE   NEW   CELL   DOCTRINE 

man  and  many  others  have  greatly  advanced  the  recogni- 
tion of  the  actual  relations.  We  know  now  that  when  an 
ovum  begins  its  development  it  must  be  regarded  as  a 
complete  cell.  This  cell  divides,  the  process  being  usually 
termed  the  segmentation  of  the  ovum.  When  the  ovum 
divides  there  arise  two  new  cells  which  then  divide  again. 
If  we  investigate  the  relations  of  such  cells  in  vertebrates 
we  may  observe  without  difficulty  that  the  cells  are  com- 
pletely isolated  from  one  another.  They  have  no  direct 
communication  between  themselves.  They  live  alongside 
one  another,  but  the  living  substance  of  one  cell  is  nowise 
united  with  the  living  substances  of  the  neighbor  cell.  In  the 
course  of  the  further  development,  however,  the  relation 
changes  because  the  cells  begin  to  unite  with  one  another. 
This  occurs  chiefly  in  two  ways.  Consequently  we  obtain 
two  kinds  of  tissues  which  we  regard  as  the  primitive  tissues  of 
the  body,  since  from  them  all  the  tissues  of  the  adult  are  slowly 


Ba 


FIG.  5. — Epithelium  (epidermis)  of  a  chicken  embryo  of  the  second  day  of  incu- 
bation. The  nuclei  are  mostly  oval  and  lie  scattered.  The  protoplasm  forms  a 
network.  There  are  no  intercellular  partitions  present.  Eph,  epitrichial  layer; 
Ba,  basal  layer. 

differentiated.  In  one  form  we  find  the  cells  completely  fused 
with  one  another  and  they  build  a  continuous  layer  which  we 
designate  as  epithelium.  In  such  a  primitive  epithelium,  Fig. 
5,  there  are  no  limits  between  the  single  cells,  but  on  the 
contrary  one  has  a  continuous  layer  of  protoplasm  in  which 
the  nuclei  are  scattered,  though  generally  rather  close  to- 


THE   NEW   CELL   DOCTRINE 


gether.     When  such  an  epithelium  grows  the  nuclei  multiply 
by  division  which  is  in  itself  a  complicated  process.     The  pro- 


FIG.  6. — Mesenchyma  of  a  chicken  embryo  of  the  third  day  of  incubation. 
Every  nucleus  is  surrounded  by  a  thin  layer  of  protoplasm  from  which  run  out  the 
strands  that  form  the  intercellular  network.  Cell  boundaries  are  not  present. 

toplasm  also  grows.     We  have  in  this  case,  therefore,  a  sub- 
stance which,  though  living,  does  not,  strictly  speaking,  con- 


schl.y 


FIG.  7. — Adult  epithelium.  Epidermis  of  Lumbricus  venetra.  jchl.  z,  mucous 
cells;  Cu,  cuticula;  J.z.,  cylinder  cells;  m.f,  muscle  fibers — below  the  epithelium.  The 
single  cells  are  separated  by  partition  walls  from  one  another. — After  M.  Heidenhain. 

sist  of  cells.     The  second  form  of  tissue  is  called  mesenchyma. 
In  mesenchyma,  Fig.  6,  one  observes  nuclei  which  are  found 


10  THE   NEW   CELL   DOCTRINE 

at  more  or  less  regular  distances  from  one  another,  and  also 
protoplasm  which  forms  an  open  network.  The  meshes  of  this 
net  contain  a  fluid,  which  is  usually  not  interpreted  as  a  part 
of  the  tissue  proper,  just  as  the  fluids,  for  example,  which  we 
find  in  the  articular  cavities  or  in  the  body  cavity  of  the  adult 
are  not  reckoned  as  tissues  of  the  body.  In  vertebrates,  in 
which  the  protoplasm  of  the  network  of  the-mesenchyma  has 
been  chiefly  studied,  we  find  that  the  network  is  at  first 
extremely  irregular;  but  early,  as  development  progresses,  the 
protoplasm  accumulates  in  parts  around  the  single  nuclei  and 

;  ',*  S 


ft 


FIG.  8. — Hyaline  cartilage  of  a  human  embryo.     Between  the  cells  the  firm  basal 
substance  of  the  cartilage  is  developed  in  large  quantities. — After  J .  Sabotta.     X  280. 

forms,  so  to  speak,  a  court  of  protoplasm  around  every  nucleus. 
From  each  court  radiate  the  threads  of  protoplasm,  which 
establish  the  connection  with  the  neighboring  courts,  and  thus 
the  mesenchyma  remains  a  network  still.  These  two  forms 
of  tissue,  which  are  characteristic  for  the  connection  or  fusion 
of  cells,  we  call  syncytium.  On  tracing  the  development 


THE    NEW   CELL   DOCTRINE  II 

further  we  learn  that  alterations  occur  so  that  we  can  observe 
the  progressive  separation  of  the  single  cells;  thus,  for  example, 
in  epithelium  there  arise  partition  walls,  Fig.  7,  separating  the 
cells  finally  and  completely  from  one  another.  In  mesen- 
chyma  the  connections  may  become  interrupted  by  which  the 
protoplasmic  masses  around  the  single  nuclei  are  joined 
together,  Fig.  8.  In  this  way  the  cells  become  completely 
isolated.  When  we  encounter  cells  which  have  been  separated 
in  this  way  we  have  to  do  not  with  a  primitive  but  with  a 
secondary  condition. 

The  descriptions  just  given  lead  us  to  one  of  the  chief  con- 
clusions of  the  new  cell  doctrine.  We  have  learned  that  the 
relations  are  much  more  complicated  than  was  previously 
assumed. 

We  turn  to  the  discussion  of  protoplasm,  or,  as  we  have 
termed  it  before,  of  the  cell  body.  It  is  necessary  to  direct  at- 
tention to  the  fact  that  in  the  living  world  we  know  two  chief 
types  of  cells;  first,  such  cells  as  exist  alone,  the  so-called  uni- 
cellular organisms.  Of  such  cells  there  are  very  many  species 
which  have  been  grouped  into  numerous  genera.  Each  genus 
and  each  species  has  its  special  peculiarities  which  we  learn 
chiefly  through  the  microscope.  When  a  cell  of  any  of  the 
just-mentioned  species  is  observed  for  a  longer  period  few  al- 
terations in  its  structure  can  be  observed.  The  chief  changes 
we  can  observe  are,  first,  an  enlargement  of  the  cell,  and  sec- 
ond, the  inner  alterations  which  are  usually  specially  notice- 
able in  the  nucleus,  which  lead  gradually  to  the  division  of  the 
cell.  The  two  new  daughter  cells  remain  extremely  similar  to 
the  original  mother  cell  in  all  peculiarities.  Such  an  organism 
propagates  itself  in  this  manner  endlessly  and  without  essen- 
tially changing  its  structure. 

Very  different  are  the  conditions  in  the  second  type  of 


12  THE    NEW   CELL   DOCTRINE 

cells,  which  we  find  only  in  the  multicellular  organisms,  that  is, 
in  the  higher  plants  and  animals.  In  them  we  observe  different 
cells  which  take  over  the  function  of  propagation.  In  the  case 
of  animals  such  cells  are  called  ova  and  spermatozoa.  A  sper- 
matozoon unites  with  an  ovum,  which  we  then  designate  as 
fertilized.  A  fertilized  ovum  is  a  complete  cell  which  divides 
and  continues  dividing  until  the  number  of  cells  for  the  con- 
struction of  an  animal  body  has  been  produced.  This  number 
may  be  enormous.  The  ovum,  or  egg-cell,  proliferates  by 
division  precisely  as  does  the  cell  of  a  unicellular  organism. 
The  cells  of  the  latter  do  not  change,  but  the  cells  which  arise 
from  the  ovum  do  change.  The  cells  of  the  multicellular  or- 
ganisms through  several  or  many  early  generations  retain  a 
relatively  similar  structure,  but  later  there  follows  a  transform- 
ation which  with  the  succeeding  generations  progresses,  and  at 
the  same  time  becomes  multifarious.  In  this  manner  the  tis- 
sues of  the  adult  arise  gradually  and  in  accordance  with  fixed 
laws. 

In  consequence  of  these  conditions  it  has  come  about  that 
we  have  derived  our  conception  of  protoplasm  and  in  part  also 
of  the  nucleus  chiefly  from  studies  which  investigators  have 
made  on  the  developing  ova,  for  in  the  early  generations  of 
these  cells  we  have  relatively  simple  relations.  Fortunately, 
however,  there  occur  among  the  unicellular  organisms  species 
which  are  comparatively  simple  in  structure,  and  which  are 
therefore  favorable  for  the  study  of  protoplasm.  If  we  wish 
to  summarize  the  result  of  numerous  investigations  in  brief 
form  we  may  say  that  we  have  learned  to  recognize  three 
conditions  of  protoplasm;  that  is,  one  condition  of  which 
we  know  as  yet  little,  but  which  is  of 'the  greatest  significance 
and  which  is  characterized  by  the  fact  that  the  protoplasm 
appears  to  us  under  the  miscroscope  absolutely  homogeneous. 


THE    NEW   CELL   DOCTRINE  13 

Homogeneous  protoplasm  is  of  the  greatest  rarity  and  as  yet 
has  been  studied  chiefly  by  the  American,  E.  B.  Wilson.3 
It  claims  our  highest  interest  because  it  represents  apparently 
the  simplest  condition  of  the  living  substance  which  we 
know.  In  the  second  state  we  find  the  protoplasm  consists 
of  two  fluids  which  exhibit  a  foam  structure,  that  is  to  say, 
the  two  fluids  are  so  mixed  together  that  one,  apparently 
the  more  fluid,  forms  droplets  and  the  other  holds  these 
droplets  apart  and  separates  them  from  one  another  com- 
pletely. As  is  well  known,  Professor  Butschli  has  specially 
studied  protoplasm  in  this  condition,  and  has  founded  the 
theory,  which  he  has  further  defended,  that  we  encounter  in 


FIG.  9. — Striated  muscle  fibers  of  a  rabbit,  colored  by  Bielschowski's  method 
and  then  teased  so  as  to  demonstrate  the  single  muscle  nbrillse. — After  a  preparation 
of  Prof .  Poll's. 

this  foam  structure  the  essential  true  fundamental  structure 
of  living  substance.  For  this  view  much  may  be  said. 
Whether,  however,  we  may  assume  that  protoplasm,  which 
is  apparently  homogeneous,  also  really  possesses  a  foam 
structure,  although  it  escapes  our  present  observation,  must 
remain  undecided.  In  its  third  condition  protoplasm  is  no 
longer  simple  because  new  structures  have  arisen  in  it  which 
are  probably  also  living,  but  which  differ  from  protoplasm 


THE    NEW   CELL   DOCTRINE 


in  appearance  and  behavior;  thus,  for  example,  if  we  study 
the  development  of  muscles,  we  find  at  first  cells  with  the 
usual  so-called  undifferentiated  protoplasm.  In  this  appear 
fine  fibers  which  we  name  fibrillae,  and  which  are  no  longer 
simple  protoplasm,  but  really  something  new,  Fig.  9.  These 
fibrils  effect  the  contraction  of  the  muscle.  They  develop 
themselves,  clearly  in  order  to  take  over  this  special  function 

of  the  muscle  cells.  Accordingly  we 
designate  the  third  condition  of  pro- 
toplasm as  the  differentiated. 

We  must  now  turn  to  a  consider- 
ation of  the  nucleus.  It  appears  in 
the  majority  of  cases  as  a  body  with 
definite  limits,  completely  surrounded 
by  protoplasm  and  with  special  sub- 
stances in  its  interior.  Usually  one 
can  distinguish  without  difficulty  a 
network,  and  in  the  meshes  of  this 
network  the  nuclear  sap.  The  net- 
work varies  extraordinarily  in  the 
single  nucleus,  but  has  one  striking 
peculiarity,  namely,  that  it  may  be 
easily  artificially  colored.  On  account 

of  this  peculiarity  the  substance  has  been  named  chromatin. 
Nucleus  differs  in  one  respect  very  noticeably  from  protoplasm, 
for  the  nuclei  develop  no  new  structures  comparable  to  those 
which  we  may  observe  in  protoplasm.  A  nucleus,  to  be  sure, 
changes  during  the  development  of  tissues  more  or  less,  but 
we  cannot  observe  new  structures  in  the  nuclei.  This  fact  is 
of  special  significance  for  the  considerations  which  are  to  be 
presented  in  the  next  following  lecture.  For  this  reason 
attention  is  now  directed  to  this  peculiarity  of  the  nucleus. 


FIG.  10. — A  vesting  nucleus 
after  ordinary  preservation 
and  staining  with  iron  hasma- 
toxyline.  From  a  cell  of  the 
intestinal  epithelium  of  a  sala- 
mander.—  After  M.  Heiden- 
hain.  Magnified  2300. 


THE   NEW   CELL   DOCTRINE  15 

Although  the  nucleus  changes  comparatively  little  during 

the  progressive  division  of  the  cell,  yet  during  the  division  of 

the  cell  matters  are 

very  different,  for 

during    every  cell       H«sa*w       "?M^W 

*-»  **  ™-        t&>  • 

cleus  passes 
through  wonderful 
t  r  a  nsf  ormations.  * 
During  these 
transform  ations 
the  sharp  limits  of 
the  nucleus  disap- 
pear, and  the  nu- 
clear substance 
gathers  together 
in  small  masses  to 
which  we  apply 
the  name  chromo- 
somes.  Each 
chromosome  di- 
vides, and  one 
piece  of  each 
chromosome 
tributes  to 
formation  of  one  of 


FIG.  ii — Red  blood  cells  of  an  embryo  duck  in  vari- 
ous stages  of  division.     The  pictures  show  the  origin, 
COn-    division  and  migration  of  the  chromosomes,  the  spindle, 
the   t^ie  reconst^tutlon  °f tne  daughter  nuclei  after  the  division 
of   the   cell  bodies. — After  M.   Heidenhain.     Magnified 


2300. 


the  new  nuclei;  the 

other  piece  to  the  formation  of  the  other  nucleus.    This  process 

may  now  be  found  exactly  described  in  the  text-books.     Every 


*  Reference  to  the  so-called  direct  division  of  cells,  or  amitosis,  is  intentionally 
omitted.  This  form  of  division  is  rare,  and  the  consideration  of  it  is  unessential 
for  our  present  purposes. 


1 6  THE    NEW   CELL   DOCTRINE 

student  of  medicine,  or  of  biology,  has  opportunity  in  his  prac- 
tical laboratory  work  to  see  for  himself  the  formations  of  the 
dividing  nucleus,  and  I  may  therefore  allow  myself  to  omit 
a  detailed  description  of  this  phenomenon.  But  there  is 
something  else  I  should  like  to  say  to  you  concerning  the 
nuclei.  It  is  now  established  that  the  nucleus  has  an  entirely 
different  chemical  composition  from  the  protoplasm.  In 
protoplasm  and  in  nucleus  we  have  to  do  cheifly  with  proteids, 
for  they  are  the  chief  components  of  both  structures.  The 
proteids  in  the  nucleus  are,  however,  in  certain  respects 
simpler  than  those  in  protoplasm.  For  this  and  other  reasons, 
it  is  believed  that  the  nutritive  material  must  first  reach  the 
nucleus  in  order  to  be  worked  over  in  the  nucleus  and  to  be 
later  returned  from  the  nucleus  to  the  protoplasm.  The 
chemical  relations  between  the  nucleus  and  the  protoplasm 
are  of  the  greatest  significance.  I  must  ask  you  to  consider 
that  I  am  not  a  competent  biological  chemist.  In  recent 
years  chemical  biology  has  made  many  beautiful  and  im- 
portant discoveries.  It  is  understood  that  we  must  seek  the 
explanation  of  most  vital  phenomena  in  the  chemical  altera- 
tions which  occur  in  the  body.  If  we  should  ever  get  so  far 
as  completely  to  understand  life  it  will  be  only  when  chemists 
are  in  a  position  to  explain  vital  phenomena  chemically.  We 
incline  to  the  belief  that  the  nucleus  is  absolutely  necessary 
to  the  functions  of  life.  It  is  besides  instructive  to  learn  that 
in  certain  lower  organisms,  in  which  we  can  distinguish  no 
definite  nucleus,  such  as  we  usually  observe,  nevertheless 
nuclear  substance  occurs  scattered  in  the  protoplasm.  From 
such  observations  we  draw  the  conclusion  that  for  the  main- 
tenance of  life  it  is  necessary  to  have  not  only  the  complicated 
protoplasm,  but  also  the  presence  of  the  differently  compli- 
cated nuclear  substance.  We  cannot  hope  to  reach  a  basis 


THE   NEW   CELL   DOCTRINE 


for  the  explanation  of  life  until  we  shall  know  how  the 
chemical  alterations  go  on  in  the  living  substance,  which 
is  a  highly  complicated  mixture  of  many  organic  combina- 
tions of  various  sorts,  all  carried  by  great  quantities  of 
water. 

A  good  example 
of  the  complica- 
tion of  the  phe- 
nomena is  offered 
us  by  the  condition 
of  the  nucleus  in 
certain  unicellular 
organisms.  In  the 
cells  of  the  highest 
plants  and  ani- 
mals the  nucleus  is 
always  a  simple 
unit,  but  there  are 
many  species  of 
protozoa  known  in 
which  the  nucleus 
is  double,  so  that 
there  appear  to  be 
two  nuclei  of  un- 

equal  size,  Fig.  12.  FIG.  12. — A  unicellular  animal,  an  infusorium  (Nassala 
T,  i  r  _j.  elegans).  Natural  length  o.i  mm.  9,  Macronucleus; 

10,     micro  nucleus. — After     Schewiakojf,     from     Lang's 
Covered     that     the    VergUichende  Anatomic. 

larger    nucleus 

plays  a  role  in  the  nutrition  and  growth  of  the  cell  while 
the  smaller  nucleus  has  assumed  exclusively  the  functions 
which  lead  to  the  division  of  the  cell.  Nature  makes  here 
for  us  an  experiment  in  that  she  has  separated  in  space  the 


7 


1 8  THE    NEW   CELL   DOCTRINE 

two  functions  of  the  nucleus,  which  are  usually  carried  out  by 
a  single  unitary  nucleus. 

Vital  phenomena  rest  on  chemical  processes  by  which 
energy  is  set  free  to  show  itself  through  the  activities  of  the 
living  being. 

The  first  thing  which  the  beginner  learns  is  that  chemical 
change,  or  metabolism,  plays  the  chief  role  in  all  biological 
phenomena.  The  biologists  describe  the  intake  and  excre- 
tion of  the  nutritive  material,  and  attempt  to  trace  the  change 
to  which  this  material  is  subjected  in  the  cell.  Cells  possess, 
of  course,  no  mouth.  They  can  absorb  material  only  through 
their  surfaces.  Therefore  the  surface  of  every  cell  is  of  the 
utmost  importance  for  the  continuation  of  its  life,  and  the 
investigation  of  this  surface  and  its  tension  has  been  eagerly 
pursued  of  late.  Important  results  have  already  been  pro- 
duced; as,  for  example,  it  has  been  discovered  that  the  surface 
tension  during  the  impregnation  of  the  ovum  must  be  changed 
if  the  spermatozoon  is  to  enter,  and  after  the  spermatozoon 
is  in  the  interior  of  the  egg  the  surface  tension  is  again  changed. 
The  gifted  German- American  investigator,  Jacques  Loeb,4 
has  advanced  the  hypothesis  that  the  egg  has  a  superficial 
layer  of  lipoid  substance  which  at  the  time  of  impregnation 
passes  into  a  soluble  condition.  This  hypothesis  has  since 
been  confirmed  by  the  experiments  of  Ralph  L.  Lillie.5 

The  egg  of  the  sea  urchin,  after  remaining  some  time  in 
sea  water,  becomes  more  resistant  so  that  the  spermatozoon 
cannot  penetrate  the  eggs  as  easily  as  when  they  were  fresh. 
If  such  resistant  eggs  are  treated  with  sea  water,  to  which  one 
has  added  0.3  per  cent,  of  ether,  by  which  supposedly  lipoid 
substances  are  dissolved,  it  is  found  that  the  eggs  are  more 
easily  fertilized.  But  even  if  Loeb's  hypothesis  is  not  ab- 
solutely correct,  the  phenomenon  itself  remains  extremely 


THE   NEW   CELL   DOCTRINE 


significant  because  we  must  assume  that  almost  incredibly 
small  quantities  of  material  occasion  alterations  in  the  ovum. 


-Ky 


,.'••> 


FIG.  13. — Muscle  nuclei  of  the  giant  salamander  (Necturus)  in  various  stages. 
A,  nucleus  of  7  mm.  larva  before  differentiation;  B,  from  a  26  mm.  larva  at  the 
beginning  of  differentiation;  C,  from  the  adult  animal,  23  mm.  long,  after  comple- 
tion of  the  differentiation. — After  A.  C.  Eycleshymer. 

So  soon  as  one  spermatozoon  penetrates  the  ovum,  as  is  found 
in  the  case  of  most  eggs,  no  spermatozoa  can  follow.     If  we 


20  THE    NEW   CELL   DOCTRINE 

study  the  phenomena  with  the  microscope  we  are  unable  to 
observe  that  anything  is  given  off  from  the  spermatozoon  to 
the  ovum.  The  changes  in  the  ovum,  therefore,  by  which 
other  spermatozoa  are  excluded  depend  upon  minimum 
quantities. 

Teleology,  or  the  adaptation  to  an  end,  rules  all  living 
bodies.  Accordingly  we  must  assume  a  priori  that  the 
limited  size  of  cells  is  a  purposeful  adaptation.  It  is  probable 
that  the  size  of  the  cells  is  favorable  to  the  metabolism  which 
occurs  chiefly  in  protoplasm.  It  depends  on  the  one  side 
upon  the  surface  of  the  cell,  and  on  the  other  upon  the  nucleus, 
which  must  itself  be  nourished  and  also  supply  material  to 
the  cell  body.  Therefore  it  is  important  that  the  distances 
remain  small.  As  an  example  of  the  relation  of  the  nucleus 
to  the  differentiation  of  protoplasm,  I  wish  to  cite  the  investi- 
gations of  Eycleshymer6  on  the  development  of  muscle  fibers. 
The  work  was  done  in  my  laboratory.  He  observed  that  the 
mass  of  chromatin  increases  in  the  nucleus  of  very  young 
muscle  fibers,  and  that  thereafter  the  formation  of  the  muscle 
fibrils  begins.  As  the  development  of  the  fibrils  progresses, 
the  amount  of  chromatin  in  the  nuclei  diminishes,  Fig. 
13.  It  is  clear  that  the  chemical  combinations  are  distrib- 
uted through  the  protoplasm  chiefly  by  diffusion,  a  slow 
process.  Hence  the  great  importance  of  the  small  dis- 
tances. A  more  exact  conception  of  this  we  may  gain  from 
the  investigations  on  the  early  development  of  pigeons, 
which  have  been  carried  out  at  the  University  of  Chicago, 
at  the  suggestions  of  Professor  Whitman.7  The  egg  of  the 
pigeon,  like  most  other  eggs,  is  fertilized  by  a  single  spermato- 
zoon. The  influence  of  this  does  not  at  first  stretch  very  far 
in  the  ovum,  so  that  the  territory  which  we  may  designate  as 
saturated  is  small.  All  around  this  territory  we  have,  so  to 


THE    NEW   CELL   DOCTRINE  21 

speak,  non-saturated  protoplasm,  into  which  a  number  of 
spermatozoa  make  their  way  and  maintain  themselves  for 
some  time,  disappearing,  however,  in  a  few  hours,  and  ap- 
parently in  the  same  measure  as  the  influence  of  the  fertiliza- 
tion proper  expands.  In  animals,  which  have  relatively 
small  eggs,  the  whole  becomes  more  rapidly  saturated  by 
fertilization,  so  that  only  one  spermatozoon  can  go  in. 

We  spoke  before  of  the  great  influence  of  small  quan- 
tities upon  the  protoplasm.  It  is  certainly  the  greatest  ad- 
vance of  modern  physiology  that  we  have  become  better 
acquainted  with  the  significance  of  this  phenomenon.  We 
have  here  to  consider  especially  a  new  kind  of  action  at  a 
distance  which  takes  place  constantly  in  our  own  bodies. 
When,  forty  years  ago,  I  made  my  first  physiological  experi- 
ments, the  nervous  system  was  the  only  means  known  to  us 
to  effect  action  at  a  distance  within  the  animal  body.  We 
studied  industriously  nerve  fibers,  sensations  in  the  brain, 
and  the  stimuli  which  passed  from  the  central  nervous  system 
to  the  various  organs  of  the  body.  Since  then  we  have  dis- 
covered the  phenomenon  of  so-called  internal  secretion.  The 
glands  form  secretions  which  are  further  used  in  the  body. 
The  majority  of  glands  have  a  duct  which  carries  off  the  se- 
cretion; thus,  for  example,  in  the  case  of  the  liver  we  have  the 
ductus  hepaticus  which  conducts  the  secretion  of  the  liver 
to  the  intestinal  canal.  It  is  known  now,  however,  that  there 
are  glands  which  have  no  duct,  Fig.  14.  Nevertheless,  these 
form  secretions  which  are  delivered  immediately  to  the  blood 
and  then  are  distributed  by  means  of  the  circulation  through 
the  entire  body.  It  has  been  learned  that  each  internal  secre- 
tion, which  is  formed  in  very  small  quantities,  exerts  a  sur- 
prisingly great  influence  on  other  parts  of  the  body  which 
may  be  quite  remote  from  the  gland.  I  may  mention  as  in- 


22 


THE    NEW   CELL   DOCTRINE 


ternal  secretions  the  products  of  the  thyroid  gland,  the  hy- 
pophysis and  the  suprarenal  bodies.  The  thyroid  gland  in- 
fluences the  condition  of  the  muscles;  the  hypophysis,  the 
growth  of  bones;  and  the  suprarenal  capsule  the  activity  of 
nerves.  In  passing  it  should  be  remarked  that  the  phenom- 
ena are  not  simple,  but  complicated.  In  all  cases,  however 
we  see  that  many  cells  of  one  kind  depend  as  to  their  structure 

jr. 


FIG.  14. — Section  of  a  thyroid  gland.  The  organ  consists  of  closed  cavities, 
each  of  which  is  bordered  by  a  layer  of  epithelial  cells.  Since  the  gland  has  no 
duct,  the  secretion  can  be  carried  off  only  by  the  blood. — After  Koelliker. 

and  their  activity  upon  the  influence  of  these  internal  secre- 
tions. It  is  not  the  case  of  a  single  cell,  but  always  of  many 
which  have  the  same  constitution. 

The  brilliant  investigations  of  Ehrlich  and  others  have 
founded  the  new  doctrine  of  immunity.  In  this  case  we 
have  to  do  with  the  phenomenon  similar  to  that  of  in- 
ternal secretion.  An  animal  becomes  poisoned  by  patho- 
genic organisms,  and  then  forms  itself  a  contra-poison,  or  so- 


THE   NEW   CELL   DOCTRINE  23 

called  antitoxin.  That  the  toxins  and  antitoxins  occur  has 
been  demonstrated  with  certainty,  but  the  quantities  are  so 
small  that  we  have  not  yet  succeeded  in  isolating  them. 
From  these  and  other  similar  phenomena  we  learn  that  the 
condition,  composition  and  structure  of  the  living  substance 
is  of  fundamental  significance,  and  is,  strictly  speaking,  more 
important  for  the  comprehension  of  vital  phenomena  than  the 
fact  that  the  physical  basis  of  life  shows  a  strong  tendency  to 
form  cells. 

We  may  now  put  into  words  the  deduction  which  we  may 
draw  from  to-day's  lecture.  Our  conclusions  may  be  ex- 
pressed as  follows: 

The  new  cell  doctrine  still  recognizes  the  importance  and 
significance  of  cells.  Cells  remain  the  units  of  morphology, 
but  from  the  physiological  standpoint  they  appear  as  adap- 
tations which,  especially  by  their  size  and  proportions,  create 
favorable  conditions  for  metabolism.  The  living  substance 
is  more  important  to  biologists  than  its  tendency  to  form  cells. 
Hence  we  consider  the  chief  problem  of  biology  to  be  the 
investigation  of  the  structure  and  chemical  composition  not 
of  cells,  but  of  the  living  substance.  The  new  conception  has 
won  its  way  gradually.  It  corresponds  to  so  fundamental  a 
change  of  our  views  that  we  are  justified  in  .describing  the 
new  conception  as  the  new  cell  doctrine. 


II. 

CYTOMORPHOSIS.* 

Your  Magnificence! 
Gentlemen! 

We  endeavored  in  yesterday's  lecture  to  familiarize  our- 
selves with  the  new  cell  doctrine,  according  to  which  a  much 
greater  importance  is  attributed  to  the  composition  of  the 
living  substance  than  to  the  fact  that  this  substance  has  a 
strong  tendency  to  form  cells;  all  the  same,  cells  remain  the 
most  convenient  units  of  biological  research,  although  they 
can  by  no  means  be  found  always  completely  separated  from 
one  another.  But  even  if  the  cells  are  not  separated,  it  is 
practical  and  convenient  to  designate  each  nucleus,  together 
with  its  surrounding  protoplasm,  as  a  cell.  Every  fully 
formed  tissue  of  the  animal  body  has  at  least  one  character- 
istic kind  of  cells,  or  in  other  words  the  cells  of  a  tissue  exhibit 
among  themselves  similar  relations  and  similar  structure. 
Hence  we  can  direct  our  attention  to  the  single  cell  which  we 
value  as  the  paradigma. 

In  man,  as  in  the  great  majority  of  multicellular  ani- 
mals, development  begins  with  simple  cells  which  arise  by  the 
segmentation  of  the  ovum.  From  the  simple  cells  the  tissues 
of  the  adult  develop  gradually.  As  I  told  you  yesterday,  we 

*  The  term  cytomorphosis  was  proposed  by  me  in  1901.  The  corresponding 
conception-  was  first  definitely  propounded  in  the  Middleton  Goldsmith  Lecture, 
published  in  1901.  This  lecture  has  recently  appeared  in  the  German  translation  in 
my  book  "Die  Methode  der  Wissenschaft"  (Gustav  Fischer,  Jena).  My  book 
"The  Problem  of  Age,  Growth  and  Death"  (New  York,  Putnam's,  1908),  treats  of 
cytomorphosis  in  some  detail,  although  in  somewhat  popular  form. 

24 


CYTOMORPHOSIS  25 

observe  no  similar  developmental  processes  in  unicellular 
organisms.  The  transformation  of  cells  which  leads  to  the 
formation  of  tissues  is  designated,  as  differentiation.  In  the 
earliest  stages  of  the  embryo  the  cells  are  remarkably  like 
one  another,  Fig.  15,  but  in  the  course  of  their  further  develop- 
ment they  become  unlike  or  different;  hence  the  designation 
differentiation.  How  these  differentiations  arise  is  an  ex- 
tremely interesting  question  about  which  we  know  very 
little,  because  as  yet  we  have  become  acquainted  almost 


FIG.  15. — Section  through  the  posterior  part  of  a  rabbit  embryo  of  seven  and 
a  half  days,  to  show  the  three  germ  layers,  each  of  which  consists  of  undifferentiated 
cells.  Magnification  250. 

exclusively  only  with  such  alterations  as  are  visible  with  the 
microscope.  The  visible  alterations,  however,  we  must 
assume,  are  the  consequence  of  chemical  processes  which  we 
still  have  to  discover.  The  visible  alterations  have  been 
studied  with  the  utmost  care  by  many  eminent  biologists, 
and  we  are  able  to  say  that  they  follow  strict  laws.  It  is 
convenient  to  have  for  the  complete  transformation  of  cells  a 
short,  scientific  term.  As  such  I  propose  "cytomofphvsis" 
We  are  now  to  occupy  ourselves  with  the  laws  of  cytomor- 
phosis  so  far  as  these  have  been  determined.  The  develop- 
ment of  simple  cells  into  differentiated  we  call  progressive 


26  CYTOMORPHOSIS 

development.  The  first  question  which  we  have  to  answer 
is:  Does  a  regressive  development  also  occur?  The  pro- 
gressive is  well  known  to  us  and  we  know  much  about  it.  I 
incline  strongly  to  the  opinion  that  it  is  the  only  kind  of 
development,  but  there  are  not  lacking  investigators  who 
have  come  to  the  belief  that  under  certain  conditions  develop- 
ment may  be  reversed. 

My  point  of  view  is  determined  in  part  by  the  fact  that 
it  has  been  possible  in  cases  where  a  regressive  development 
had  been  assumed  to  make  sure  by  careful  investigation  that 
opinion  had  been  misled  by  appearances  and  that  in  reality 
the  development  was  progressive  in  these  cases  also.  I  may 
mention  three  examples;  first,  the  nerve  fibers.  If  one  cuts 
through  a  nerve,  the  fibers  in  its  peripheral  part  degenerate 
quite  rapidly.  After  several  days,  however,  under  favorable 
conditions,  newly  formed  nerve  fibers  appear  in  the  peripheral 
part.  Many  investigators  have  eagerly  advanced  the  view 
that  these  nerve  fibers  rise  in  their  place  and  that  they  have 
been  newly  formed  in  the  degenerating  nerve.  More  careful 
research  has  made  it  certain  that  the  newly  formed  fibers 
have  simply  grown  out  upon  the  ends  of  the  healthy  fibers, 
left  in  the  central  part  of  the  nerve.  If  one  cuts  off  the  roots 
of  a  tree,  the  roots  which  are  separated  from  the  trunk 
decay;  but  if  the  tree  is  left  one  can  find  later  in  their  place 
living  roots,  which,  however,  have  not  arisen  from  the  dying 
roots,  but  have  grown  out  from  the  central  healthy  parts. 
The  fundamental  experiments  of  Harrison8  make  it  sure 
that  nerve  fibers  in  all  cases  are  formed  only  in  the  way 
mentioned.  About  the  origin  of  nerve  fibers  there  has  been 
a  long  controversy.  My  countryman,  Harrison,  has  occupied 
himself  for  several  years  with  this  question,  and  has  supported 
his  conclusion  by  the  most  varied  investigations.  Four 


CYTOMORPHOSIS  27 

years  ago  he  invented  a  new  method  to  keep  isolated  cells 
and  pieces  of  tissue  living  in  vitro.  Utilizing  the  new  method, 
he  subjected  young  nerve  cells,  neuroblasts,  to  observation 
and  was  able  to  see  under  the  microscope  nerve  fibers  grow 
out  from  the  living  cell.  Cultures  in  vitro  are  now  made 
frequently,  and  we  expect  from  the  application  of  Harrison's 
ingenious  method  many  valuable  discoveries.  From  time 
to  time  we  find  the  paradox  justified  which  says:  "New 
methods  are  more  important  for  science  than  new  thoughts.77 


> 


7 

^ 

I 

] 

Jt 

/ 

1   ' 

'fi 

FIG.  1 6. — Degenerating  muscle  fibers  after  experimental  injury,  a,  b,  after 
3  days;  c,  after  8  days;  d,  26  days;  e,  10  days;  /,  21  days;  g,  43  days.— 4f/er  Erws* 
Ziegler. 

The  second  example  we  get  from  muscles.  If  the  fibers  of 
a  skeletal  muscle  are  mechanically  injured  they  degenerate 
quickly;  later,  however,  we  find  new  formed  muscles.  Here 
the  processes  are  of  quite  a  peculiar  sort.  Every  muscle 
fiber  consists  chiefly  of  muscular  substance  which  we  can 
easily  demonstrate  by  the  contractile  fibrils.  It  is  the 


28  CYTOMORPHOSIS 

muscular  substance  which  breaks  down  after  the  injury. 
The  muscle  fibers,  however,  contain  also  the  so-called  muscle 
corpuscles,  which  are  nothing  more  than  little  accumulations 
of  undifferentiated  protoplasm,  containing  the  nucleus, 
Fig.  16.  After  the  injury  these  corpuscles  do  not  degenerate, 
so  that  undifferentiated  protoplasm  remains  from  which  the 
new  formation  starts.  The  differentiated  part  of  the  muscle 
disappears  and  there  is  in  this  case  no  question  of  a  regressive 
development. 


FIG.  17. — ^Longitudinal  section  of  the  regenerating  extremity  of  a  young  lobster 
one  day  after  amputation.  There  is  formed  at  first  a  blood  clot  (bd)  under  which 
the  epithelial  cells  e,  e',  grow  across  to  form  the  commencement  of  the  new  part. 
Magnification  240. — After  V.  E.  Emmel. 

The  third  example  we  will  take  from  the  lobster.  If  the 
extremities  of  the  larvae  of  this  animal  are*  cut  off,  the  ex- 
tremities will  be  newly  formed.  It  was  formerly  assumed 
that  we  had  to  do  in  such  a  case  with  a  new  regressive  develop- 
ment. The  investigation  made  by  Emmel 10  in  my  laboratory 
has  rendered  the  real  history  clear.  The  cells  of  the  outer- 
most layer  of  the  skin  in  these  larvae  are  undifferentiated  cells, 
which  after  the  injury  grow  and  spread  over  the  wounded 
surface.  They  then  multiply  and  by  their  steady  growth 


CYTOMORPHOSIS  29 

create  the  new  extremity.  Afterward  they  differentiate 
themselves  in  part  in  order  to  form  the  various  tissues  which 
are  characteristic  for  the  limbs  of  Crustacia,  Fig.  17.  The 
nerves  and  probably  the  blood-vessels  penetrate  subsequently 
into  the  newly  formed  extremity.  To  conclude:  Until  it  is 
shown  in  at  least  one  case  with  absolute  certainty  that 
regressive  development  occurs  it  must  remain  very  improbable 
in  the  minds  of  earnest  biologists  that  such  a  development 
occurs  at  all,  or  can  occur. 

Cytomorphosis  defines  comprehensively  all  structural 
relations  which  cells  or  successive  generations  of  cells  undergo. 
It  includes  the  entire  period  from  the  undifferentiated  stage 
to  the  death  of  the  cell.  The  differentiations  which  occur  in 
the  body  are  very  different  among  themselves,  and  as  is 
well  known  these  differences  are  much  greater  in  the  higher 
than  in  the  lower  animals.  Hence  it  is  by  no  means  easy  to 
recognize  at  once  what  is  common  to  these  changes,  but  some 
important  results  have  already  been  won.  First  of  all  it  is 
to  be  stated  that  the  differentiation  in  all  cases  shows  itself  by 
visible  new  functioning  structures  in  the  protoplasm.  There 
exists  here  between  the  protoplasm  and  the  nucleus  a  marked 
contrast,  for,  as  you  have  learned,  the  nucleus  acquires,  strictly 
speaking,  no  new  structures,  although  it  also  changes  with  the 
progressive  development. 

We  know  that  the  visible  alterations  in  protoplasm  are 
initiated  by  invisible  ones.  Various  experiments  afford  the 
proof  of  this.  The  first  rudiment  of  the  fore-leg  of  the 
larva  of  an  amphibian  may  be  cut  off  and  then  grafted  into 
another  part  of  the  body,  where  the  rudiment  will  develop 
further.11  The  rudiment,  or  anlage,  at  the  stage  which  is 
specially  suited  to  this  experiment,  is  a  little  bud  on  the 
surface  of  the  larva.  Microscopic  examination  shows  that 


3O  CYTOMORPHOSIS 

its  cells  are  simple  and  more  or  less  similar  to  one  another.^ 
Tissues  in  the  stricter  sense  are  not  present.  In  spite  of  the 
fact  that  these  cells  attain  their  further  development  under 
unnatural  conditions  they  in  themselves  form  muscle  fibers, 
connective  tissue  and  bone.  In  spite  of  the  fact  that  the 
microscope  shows  us  nothing  in  these  cells  by  which  we  can 
recognize  their  future  development,  we  must  assume  that 
the  specification  already  exists.  Professor  Harrison,  as  I 
have  already  mentioned,  devised  a  method  to  cultivate  tissues 
in  vitro.  One  can  cut  out  from  an  embryo  chick  little  pieces 
at  will  and  cultivate  them  artifically  in  vitro  and  bring  them 
to  further  development.  In  this  manner  W.  H.  Lewis  has 
succeeded  in  studying  the  specific  cell  formation.  The 
cells  of  the  mesenchyma  grow  in  the  manner  of  mesenchyma ; 
the  cells  of  epithelium  as  epithelium.  Neither  in  the  nucleus 
nor  in  the  protoplasm  in  these  cells  can  we  demonstrate 
peculiarities  which  we  can  regard  as  the  causes  of  the  unlike- 
ness  of  their  growth,  but  surely  there  exist  in  these  cells 
peculiarities  which  are  not  visible  to  us  and  which  determine 
the  performances  of  the  cells.  It  is  not  going  too  far  to 
assume  that  in  all  cases  the  invisible  alterations  of  protoplasm 
precede  the  visible. 

The  young  cells  in  an  undifferentiated  vertebrate  embryo 
have  little  protoplasm.  The  first  thing  that  must  happen  is 
that  the  protoplasm  grows,  a  phenomenon  which  one  may 
easily  observe  with  the  microscope.  After  the  protoplasm 
has  grown,  differentiation  proper  may  begin.  It  is  always 
gradual  and  consists  essentially  in  this,  that  something  new 
becomes  visible  in  the  protoplasm.  In  part,  especially  in  the 
so-called  epithelium,  we  have  to  do  with  the  formation  of 
superficial  membranes  around  each  cell.  More  important 
probably  are  the  new  formations  in  the  protoplasm,  Fig.  18. 


CYTOMORPHOSIS  31 

The  developing  nerve  fibrils  I  have  already  mentioned.  In 
nerve  cells  there  appear  very  fine  fibers  which  develop  grad- 
ually, making  a  network  in  the  cell,  Fig.  19.  There  also  appear 
deposits  of  a  substance  which  reacts  to  stains  differently  from 
the  protoplasm  and  the  fibrils,  Fig.  18,  k,  k'.  The  deposits  in 
question  have  received  the  somewhat  fantastic  name  of  "tig- 


Ax 


FIG.  18. — Motor  nerve  cells  from  the  spinal  cord  of  a  rabbit,     ke,  nucleus;  den, 
dendrite;  Ax,  nerve  fiber,  and  x,  its  origin;  k,  kf,  Nissl  bodies. — After  K.  C.  Schneider. 


roid  substance."  We  notice  also  peculiar  cavities  which  form 
a  net- work  in  the  protoplasm  of  the  cell,  and  are  filled  with 
fluid.  In  the  gland  cells  one  sees  the  material  distributed  in 
the  protoplasm  which  is  utilized  later  for  the  execution  of  the 
specific  activities  of  the  gland  cells,  Fig.  20  This  material  is 
not  the  secretion  proper,  but  a  primary  stage.  In  quite 
another  wise  do  the  intervening  supporting  tissues  develop, 
for  in  them  the  cells  show  a  strong  tendency  to  separate  from 
one  another  and  to  produce  special  structures  in  the  inter- 


32 


CYTOMORPHOSIS 


cellular  spaces.     It  is  not  practicable  to  lay  further  illustra- 
tions before  you. 

Progressive  development  is  closely  connected  with  another 

phenomenon.  The 
embryonic  tissues 
grow  with  immense 
rapidity,  the  differen- 
tiated tissues  on  the 
contrary  grow  slowly. 
If  we  investigate  the 
conditions  more  care- 
fully we  learn  that  the 
cells  gradually  lose 
the  power  of  division 
as  they  are  differen- 
tiated. If  the  differ- 
entiation progresses 
far,  then  probably  the 
capacity  of  division  is 
lost  to  the  cells  alto- 
gether. Formerly  we 
had  no  exact  concep- 
tion of  the  rapidity  of 
growth  in  embryos. 
This  is  a  question 
about  which  I  have 
been  greatly  interested 
for  many  years.  In 
the  book  "  The  Prob- 
lem of  Age,  Growth 
and  Death,"  which  I 
published  in  1908,  I 


FIG.  19. — Nerve  cell  from  the  spinal  cord  of 
man.  The  Nissl  bodies  have  been  dissolved  out 
and  the  cell  so  colored  that  the  neurofibrils  are 
brought  out.  fi,  fibrils;  x,  fibrils  in  a  dendrite;  ax, 
nerve  fiber;  lu,  space  left  by  the  dissolving  of  the 
Nissl  bodies;  ke,  nucleus. — From  K.  C.  Schneider, 
after  Bethe. 


CYTOMORPHOSIS 


33 


have  discussed  more  fully  the  alterations  of  the  rapidity  of 
growth  with  age  and  its  relation  to  the  increase  of  differentia- 
tion. The  development  of  a  mammal  begins  with  an  extra 
power  of  growth.  How  gradual  the  increase  is  it  is  not  yet 
possible  to  determine  exactly,  but  certainly  the  original  daily 
increase  is  not  less  than  1000  per  cent.  This  holds  true  for 
man  also. 

Immediately  after  birth  one  finds  the  highest  rapidity  in 
the  rabbit  to  be  not  quite  18  per  cent,  per  day;  in  the  chick 
not  quite  9,  and  in  the  schs.i 

guinea  pig  about  51/2  per 
cent.  The  relations  for 
man  are  similar.  It  is 
therefore  clear  that  the 
animals  mentioned  and 
man  also  have  lost  at  the 
time  of  their  birth  99  per 
cent,  of  their  original 
growth  capacity.  In  fact, 
from  the  biological  stand- 
point we  are  really  old  by 
the  time  we  are  born  and 
the  alterations  which  make 
us  old  have  for  the  most 
part  already  occurred.  The  further  losses  which  we  suffer 
from  birth  to  old  age  are  comparatively  small,  and  we  live 
long  only  because  these  losses  take  place  slowly.  If  the 
progress  of  alteration  after  birth  should  be  even  only 
approximately  as  swift  as  before  birth  we  should  live  only 
a  very  short  time.  And  in  fact  the  microscope  shows  us 
that  the  multiplication  of  cells  after  birth  is  by  no  means  so 
great  as  before,  and  that  it  goes  on  slowly. 


ke 

FIG.  20. — Cell  from  the  pancreas  of  the 
larva  of  Salamandra  maculosa.  sec.  k, 
sec.  kf,  secretory  granules;  x,  formative 
focus  of  the  same;  fi,  secretory  fibrils;  ke, 
nucleus;  schs.  i,  closing  plate. — After  K.  C. 
Schneider. 


34  CYTOMORPHOSIS 

Cytomorphosis  includes  more  than  differentiation  proper. 
By  continuing  it  leads  to  the  degeneration  of  the  cell.  De- 
generation appears  in  many  cases  to  depend  upon  the  trans- 
formation of  the  entire  protoplasm  so  that  no  more  true 
protoplasm  remains  in  the  cell.  Under  such  conditions  the 
cells  do  not  remain  viable.  A  good  example  of  this  process 
is  afforded  by  the  epidermis,  the  outer  skin,  the  lowest  layer 
of  which  consists  of  undifferentiated  cells,  which  can  grow  and 
multiply,  Fig.  22.  Some  of  these  cells  liberate  themselves 
from  their  parent  layer  and  migrate  toward  the  surface. 
During  their  migration  their  protoplasm  is  gradually  changed 
into  horny  substance,  and  when  this  change  is  complete  the 
cells  have  completed  their  cytomorphosis  and  are  dead.  The 
surface  of  our  body  is  covered  by  dead  cells.  In  this  case  as 
in  all  similar  cases  degeneration  leads  to  the  death  of  the  cell. 
We  can  accordingly  distinguish  four  chief  stages  of  cytomor- 
phosis. 

1.  Undifferentiated  or  embryonic  condition. 

2.  Differentiation. 

3.  Degeneration. 

4.  Death. 

Only  in  this  succession  can  alterations  of  cytomorphosis 
occur,  but  it  must  be  added  that  if  regressive  development 
should  occur  it  would  form  an  exception  to  this  rule. 

The  red  blood- corpuscles  afford  us  an  excellent  example  of 
a  complete  cytomorphosis.  They  begin  their  development 
as  simple  cells,  with  a  well  formed  nucleus  but  little  proto- 
plasm. Next  we  observe  that  the  protoplasm  grows.  Not 
until  it  has  grown  sufficiently  does  it  acquire  its  character- 
istic color  through  the  formation  of  hemoglobin,  thus  be- 
coming a  young  red  blood-corpuscle  which  may  still  grow  a 


CYTOMORPHOSIS  35 

little,  although  the  nucleus  at  the  same  time  begins  to 
grow  smaller.  After  the  nucleus  has  become  considerably 
smaller  it  is  separated  from  the  body  of  the  corpuscle.  As  to 
how  this  separation  occurs  authorities  are  still  disputing.  The 
part  left  without  the  nucleus  is  the  so-called  mature  blood- 
corpuscle  which,  however,  is  not  able  to  maintain  its  own 
but  soon  breaks  down.  Every  day  in  each  of  us  numberless 
millions  of  blood-corpuscles  are  disappearing.  The  car- 
tilaginous cells  also  pass  through  a  complete  cytomorphosis 
which,  when  the  cartilage  is  replaced  by  bone,  terminates  with 
the  dramatic  disappearance  of  the  cells.  Cartilage  is  devel- 
oped from  embryonic  mesenchymal  cells.  The  cells  enlarge 
and  there  appears  between  them  the  basal  substance  which 
imparts  to  cartilage  its  characteristic  physical  consistency, 
Fig.  8.  The  so-called  ossification  of  cartilage  begins  with  the 
completion  of  the  chondral  cytomorphosis,  during  which  the 
cells  pass  through  rapid  degenerative  hypertrophy,  Fig.  21, 
which  involves  the  destruction  of  the  basal  substance,  and 
which  closes  with  the  disintegration,  or  autolysis,  of  the  cell. 
Thereupon  bone  is;  formed  in  the  place  of  the  cartilage  which 
has  disappeared.  (  The  nerve  cells,  at  least  in  vertebrates, 
pass  through  their  cytomorphosis  in  a  special  tempo.  Their 
differentiation  advances  quite  early  to  the  high  point  at 
which  the  cells  long  remain.  The  degenerative  alterations 
follow  very  slowly,  so  that  we  usually  do  not  encounter  mental 
weakness  in  man  until  advanced  age,  the  weakness  being 
caused  by  senile  atrophy  of  the  brain  cells.  We  are  in- 
debted to  the  peculiar  course  of  the  cytomorphosis  of  the 
brain  for  the  extraordinarily  long-lasting  functional  capacity 
of  this  organ.  The  leaves  of  plants  offer  us  an  excellent 
example  of  cytomorphosis.  The  leaf  bud  consists  of  em- 
bryonic cells  which  grow  and  differentiate  themselves  to 


CYTOMORPHOSIS 


form  the  leaf.     Later  the  cells  degenerate  and  die.     The  leaf 
becomes  dead  and  falls.     It  would  be  easy  to  lay  before 


-Pa 


FIG.  21. 


FIG.  22. 


FIG.  21. — Cytomorphosis  of  the  cartilage  cells.  From  a  section  of  the  vertebral 
arch  of  a  pig  embryo,  a-e,  successive  stages;  in  e,  the  letters  kn  refer  to  the  limit  of 
the  cavity  which  is  no  longer  filled  by  the  degenerating  cell. 

FIG.  22. — Epidermis  from  the  sole  of  the  domestic  cat.  Ba.  Schi,  basal  germ 
layer;  Hor.  La,  hor.  z,  hor.  z',  horny  layer  formed  by  dead  cells;  ker.  k,  layer  of  cells 
which  are  being  cornified;  Ml.  La,  middle  layer  of  cells  which  are  migrating  upward 
and  at  the  same  time  enlarging;  Pa,  site  of  a  hypodermic  papilla. — After  K.  A .  Schnei- 
der. 


CYTOMORPHOSIS  37 

you  many  other  examples  of  completed  cytomorphosis  of  the 
most  various  cells.  It  might,  however,  be  better  to  pass 
over  to  other  considerations. 

Death  and  subsequent  removal  of  cells  play  a  great  role 
in  our  lives.  Even  in  early  developmental  stages  we  find  cells 
dying  and  even  whole  organs  which  maintain  themselves  only 
for  a  certain  period  and  then  disappear  almost  or  completely. 
Thus  there  is  an  embryonic  kidney  in  which  only  small  re- 
mains can  be  found  in  the  adult.  It  is  therefore  clear  that 
there  must  be  some  arrangement  provided  to  make  good  the 
loss  of  cells.  Nature  accomplishes  this  by  not  bringing  all 
cells  to  further  development  and  by  preserving  a  stock  of  less 
differentiated  cells  in  the  body.  Of  these  I  have  already 
mentioned  an  example,  the  epidermis,  the  cells  of  the  under 
layer  of  which  preserve  an  embryonic  character.  Only  by  the 
presence  of  these  cells  which  keep  the  essential  embryonic 
type  is  the  continual  renewal  of  the  epidermis  made  possible. 
For  every  hair  there  remains  a  special  group  of  embryonic  cells 
upon  the  hair  papilla,  which  provide  for  the  growth  of  the 
hair.  Since  these  cells  are  not  differentiated,  they  can  multi- 
ply and  thus  furnish  cells  for  the  formation  of  the  hair.  The 
cells  of  the  hair  complete  their  cytomorphosis,  but  their  sister 
cells  remain  on  the  papillae  undifferentiated.  We  thus  see 
that  while  cytomorphosis  can  go  on  only  in  the  one  direction, 
it  remains  true  that  the  cytomorphosis  can  be  arrested  and 
that  it  may  go  on  in  the  different  tissues  with  unequal  rapidity. 
Thus  it  comes  that  we  encounter  cells  in  the  adult  animal  in 
every  possible  stage  of  cytomorphosis.  There  arise  in  every 
one  of  us  every  day  cells  which  complete  their  cytomorphosis, 
and  there  are  others  which  have  hardly  begun  it.  We  cannot 
understand  the  relations  in  the  adult  animal  if  we  do  not 
consider  at  once  both  the  daily  dying  off  of  old  cells  and 


38  CYTOMORPHOSIS 

also  the  daily  multiplication  of  cells  which  have  remained 
embryonic. 

We  recognize  that  the  embryonic  cells  are  of  great  impor- 
tance not  only  during  the  embryonic  period,  but  also  in  the 
adult.  How  great  this  importance  is  is  revealed  in  the  inves- 
tigation of  regeneration.  Very  many  animals,  if  parts  of 
their  body  are  removed,  will  form  the  missing  parts  anew.  If, 
for  example,  we  break  off  the  tip  of  the  tail  of  a  lizard,  there 
will  arise  a  new  tip  which  is  formed  by  the  growth  of  undif- 
ferentiated  tissues.  There  are  worms  which  multiply  by 
forming  in  the  middle  of  their  bodies  the  so-called  budding 
zone.  Karl  Semper13  has  studied  the  process  in  annelids, 
and  discovered  that  in  them  the  budding  zone  consists  of  cells 
of  the  embryonic  type.  Gradually  these  cells  advance  in 
their  cytomorphosis,  and  so  there  arises  a  new  tail  for  the 
anterior  part  of  the  worm  and  a  new  head  for  the  posterior 
part,  and  thereupon  the  two  parts  separate  and  two  complete 
works  have  arisen  from  the  single  animal.  We  are  accustomed 
to  designate  those  animals  which  have  a  more  complicated 
structure  as  the  higher.  Now  it  is  clear  that  if  an  animal  is 
composed  of  relatively  few  cells  great  complexity  of  structure 
is  impossible.  Further  we  observe  that  when  a  highly  formed 
animal  is  to  be  produced,  nature  takes  care  that  a  large 
number  of  embryonic  cells  is  produced.  In  the  lower  animals 
development  is  of  the  so-called  larval  type.  From  the  little 
ovum  there  arises  quickly  a  young  animal  which  lives  free 
and  must  take  care  of  itself.  Such  a  larva  must  possess,  even 
if  only  in  simple  form,  all  the  principal  organs,  and  since  the 
cells  must  be  so  far  differentiated  that  they  can  take  over  the 
various  functions,  they  necessarily  lose  in  part  their  capacity 
to  multiply,  and,  what  is  still  more  important,  the  capacity 
to  produce  other  kinds  of  cells.  We  see  always  that  when 


CYTOMORPHOSIS  39 

a  cell  has  begun  to  develop  in  one  direction  it  cannot  start 
out  to  develop  in  any  other  direction.  In  the  higher  animals, 
on  the  contrary,  we  find  a  relatively  large  egg  which  has  become 
large  through  the  storing  up  in  it  of  yolk  or  nutritive  material. 
The  developing  ovum  can  nourish  itself  for  a  long  time  from 
this  yolk.  In  this  type  of  development  we  encounter  not 
larvae  but  embryos  which  are  characterized  thereby  that  they 
contain  many  cells  of  the  embryonic  or  undifferentiated  type. 
These  cells  assume  definite  groupings  to  form  the  rudiments 
or  anlages  of  the  various  organs.  So  that  we  may  say  that 
the  anatomical  development  progresses  without  there  being 
a  corresponding  alteration  in  the  structure  of  the  single  cells. 
Thus  we  observe  in  the  human  embryo  the  stomach,  or  other 
organ,  which  shows  the  essential  characteristics  of  its  total 
form  and  of  its  relations  to  other  parts  of  the  body,  and  yet 
consists  of  cells  not  differentiated.  In  my  opinion  we  are 
justified  in  regarding  the  embryonic  development  as  a  con- 
trivance to  make  the  postponement  of  a  cytomorphosis  pos- 
sible, in  order  that  the  total  number  of  cells  available  for 
differentiation  shall  be  larger.  Of  the  great  importance  of 
the  number  of  cells  we  can  get  some  notion  by  considering  the 
cortex  of  the  brain.  The  number  of  pyramidal  cells  in  the 
cerebral  cortex  of  man  is  over  4,000,000,000.  This  number 
is  not  astonishing;  a  cubic  millimeter  of  blood  contains  be- 
tween four  and  five  million  corpuscles. 

The  purpose  of  differentiation  is  known.  Every  living 
cell  certainly  carries  on  all  the  essential  functions  of  life.  In 
the  higher  organisms  we  encounter  a  division  of  labor. 
Each  organ  takes  over  as  its  special  task  one  or  another 
function,  which  the  organ  performs  to  the  advantage  of  the 
whole.  These  functions  are  not  new;  they  are  always  such 
as  are  common  to  the  living  substance  in  general,  and  in 


40  CYTOMORPHOSIS 

each  single  organ  there  comes  about,  so  to  speak,  an  exaggera- 
tion of  a  single  function.  Protoplasm  is  sensitive  and 
irritable.  In  our  case,  our  sense  organs  take  care  of  the 
sensations  to  the  advantage  of  the  whole  body.  Protoplasm 
has  contractility,  and  this  function  is  assumed  by  the  muscles 
again  to  the  advantage  of  the  whole  body.  Similarly,  the 
glands  take  over  the  formation  of  secretions — the  excretory 
organs,  the  elimination  of  urea,  etc.  Now  we  know  that  the 
various  structures  which  we  can  see  in  protoplasm,  and  which 
are  characteristic  for  the  sense  organs,  muscles,  gland  cells, 
etc.,  determine  in  each  case  the  special  performances  of  their 
respective  cells.  Briefly  expressed,  the  whole  meaning  of 
differentiation  is  physiological.  The  peculiarities  which  we 
can  recognize  with  the  microscope  in  differentiated  cells  exist 
in  order  to  render  it  possible  for  the  cells  to  accomplish 
their  special  activity.  It  would  be  superfluous  to  linger  over 
this  conception,  to  amplify,  or  even  to  justify  it  by  a  rounda- 
bout demonstration.  I  wish,  however,  to  specially  emphasize 
the  fact  that  the  entire  doctrine  of  cytomorphosis  renders 
it  clear  that  structure  in  living  substance  is  the  essential 
thing.  This  has  become  clear  to  us  from  the  phenomenon  of 
differentiation.  We  may  probably  go  still  further  and  say 
that  even  in  those  cases  in  which  we  as  yet  cannot  recognize 
any  microscopic  structure,  structure  is  still  present.  The 
conception  of  the  significance  of  structure — of  organization, 
which  we  win  from  the  investigation  of  differentiated  cells, 
applies  also  to  protoplasm.  It  is  well  known,  as  I  have 
already  mentioned,  that  protoplasm  is  chemically  extremely 
complicated,  but  the  chemical  combinations  are  not  simply 
mixed  together  as  in  a  simple  solution,  but  are  in  part  sepa- 
rated spatially.  When  we  state  that  the  living  substance 
has  organization  we  base  our  view  not  only  on  the  application 


CYTOMORPHOSIS  41 

of  that  notion  of  structure  which  we  derive  from  the  study  of 
differentiated  cells,  but  also  on  direct  observation.  Such 
investigation  has  not  yet  brought  us  very  far.  It  teaches  us 
that  protoplasm  is  not  completely  uniform,  but  usually 
contains  fine  granules  which  are  unlike  among  themselves. 
Micro-chemistry  is  a  nascent  science  from  which  we  may 
expect  much,  although  she  has  presented  us  yet  with  but  little. 
It  is  the  science  which  investigates  the  chemical  substances 
and  processes  in  cells  with  the  help  of  the  microscope.  We 
have  already  succeeded  in  proving  that  granules,  chromidia, 
fatty  substances,  lipoids  and  various  proteids  exist  in 
protoplasm  in  a  visible  form.  We  have  also  learned  through 
micro-chemistry  something  of  the  distribution  of  iron  and 
phosphorus  in  the  cell.  We  have  not  yet  got  very  far,  but 
far  enough  to  be  justified  in  saying  that  the  organization  of 
living  substance  is  known  in  part  by  direct  observation. 

We  are  acquainted  with  another  structure  in  the  proto- 
plasm of  many  cells,  the  so-called  centrosome  which  we  can 
only  allude  to  here,  although  its  occurrence  again  demon- 
strates the  importance  of  organization. 

A  word  more  concerning  the  nucleus.  In  the  nucleus 
organization  can  be  observed  easily  and  without  exception, 
and  since  the  nucleus  also  belongs  with  the  living  substance, 
its  peculiarities  also  serve  to  strengthen  us  in  the  belief  in 
the  importance  of  organization.  Whoever  knows  the  won- 
derful history  of  the  chromosomes  by  his  own  observation, 
must  be  convinced  that  the  nucleus  has  a  very  complicated 
organization. 

Now  to  the  conclusion.  Cytomorphosis  is  the  funda- 
mental conception  of  the  entire  development  of  all  multi- 
cellular  organisms,  and  is  the  foundation  at  once  of  morph- 
ology and  physiology.  It  explains  to  us  many  processes 


42  CYTOMORPHOSIS 

which  we  otherwise  could  not  understand.  It  includes  the 
whole  doctrine  of  the  normal  and  pathological  differentiation 
of  cells.  The  principal  conclusion  which  we  may  deduce  from 
this  doctrine  is  that  all  living  substance  possesses  an  organiza- 
tion, and  that  probably  without  organization  life  is  impossible. 


III. 

THE  DOCTRINE  OF  IMMORTALITY. 

Your  Royal  Highnesses! 

To  your  Royal  Highnesses  I  wish  to  express  my  profound 
and  respectful  thanks  for  the  honor  of  your  presence,  which 
has  for  me  a  great  and  unforgetable  significance.  The  partici- 
pation of  your  Royal  Highnesses  in  to-day's  lecture  is  a  high 
distinction  not  only  for  me  but  for  my  university,  which  we 
gratefully  acknowledge. 

Everything  living  arises  only  from  the  living.  The  phe- 
nomenon of  propagation  of  animals  and  of  plants  has  always 
excited  the  interest  of  mankind.  The  ancients  recognized 
that  only  living  parents  could  have  a  living  progeny,  and  it 
was  said  "Omne  vivum  ex  vivo."  But  for  a  long  time  the 
opinion  prevailed  that  life  might  continually  arise  anew.  We 
know  now,  however,  with  certainty  that  a  new  generation  of 
this  kind  does  not  occur,  and  assume  that  under  present  con- 
ditions a  new  generation  of  life  is  improbable,  perhaps  impos- 
sible. We  know  too  little  to  venture  a  positive  opinion. 
Schaefer,15  the  gifted  physiologist  of  Edinburgh,  has  expressed 
a  supposition  that  new  generation  still  occurs  upon  our  earth 
and  escapes  our  observation  because  we  do  not  know  the  con- 
ditions which  render  such  generation  possible.  This  is  an 
interesting  speculation,  but  with  this  possible  exception  we 
must  attribute  to  the  saying,  " omne  vimim  ex  vivo"  absolute 
validity. 

With  the  progress  of  our  knowledge  we  have  made  interest- 
ing discoveries  concerning  the  manner  in  which  the  uninter- 

43 


44  THE   DOCTRINE    OF   IMMORTALITY 

rupted  continuation  of  the  living  substance   is  assured  in 
various  organisms.     The  simplest  cases  occur  in  the  lower 
organisms,  in  bacteria,  etc.,  in  unicellular  plants  and  ani- 
mals.      In  these  the  single  individual,  or  the  single  cell, 
grows  up  to  a  certain  size  and  then  divides.     In  this  man- 
ner the  two  daughter  cells  come  to  have  part  of  the  same 
substance   as   the   mother  cell,  and  so  it  goes  on.       This 
substance,    so  far   as    we    can    observe,    does    not    change 
essentially  with  time.      In  the  higher  plants  and  animals 
we  have  in  each  case  to  do  with  many  cells  and  we  observe 
that  the  functions   are  unequally  distributed  among  these 
cells.     For  the  execution  of  various  functions  the  cells  become 
unlike  among  themselves.     This  is  the  phenomenon  of  dif- 
ferentiation of  which  we  have  already  spoken.     The  majority 
of  the  cells  are  destined  for  the  care  of  the  whole,  and  perform 
their  special  functions.     Some  of  the  cells,  however,  are  not 
utilized  in  this  manner,  but  serve  for  propagation.      When 
a  flower  unfolds  in  our  garden  we  find  in  it  certain  special  cells 
which  have  to  do  with  the  propagation.     These  do  not  show 
such  differentiation  as  we  may  find  in  other  cells  of  the  plant, 
but  remain  at  first  relatively  simple  in  their  structure.     The 
propagating  cells  mentioned  separate  themselves  from  the 
mother  plant  and  form  the  seed.     As  essential  in  this  case 
it  appears  that  two  cells  are  necessary  for  the  process,  one  of 
which  we  designate  as  the  egg  cell  and  the  other  as  the  seminal 
cell.     Two  such  cells  unite  and  form  a  new  cell,  with  which 
the  further  development  begins.     The  mother  plant  may 
then  die.     We  note  in  this  case  that  the  fate  of  the  cells  is 
extremely  unlike,  in  that  some  of  them  are  given  over  to  death, 
while  others  remain  permanently  alive  and  serve  for  the 
propagation  of  the  species.     In  the  next  lecture,  in  which  we 
shall  investigate  the  development    of  death,  we  shall  occupy 


THE   DOCTRINE    OF   IMMORTALITY  45 

ourselves  with  the  consideration  of  the  phenomenon  of  death. 
At  present  we  shall  devote  our  attention  to  the  propagating 
of  cells. 

The  kind  of  propagation  which  we  find  in  the  plant  is 
called  sexual  and  occurs  also  in  animals.  It  is,  however,  by 
no  means  necessary  that  the  propagation  should  occur  by 
sexual  means.  Of  the  methods  which  nature  applies  for  the 
multiplication  of  living  individuals,  I  should  like  to  mention  a 
few  to  you  briefly. 

Many  methods  of  asexual  reproduction  are  known  to  us. 
The  art  of  increasing  plants  in  this  way  is  practiced  by  every 
gardener,  and  nature  also  makes  use  of  the  possibilities. 
Among  animals  we  often  find  a  multiplication  of  individuals 
effected  by  simple  division.  The  zoologist  describes  to  us 
the  column-like  growth  of  certain  jelly-fish  and  the  following 
transverse  division  of  the  column,  so  that  a  number  of  discs 
arise,  each  of  which  becomes  a  jelly-fish.  Asexual  reproduc- 
tion occurs  among  invertebrates  in  various  forms.  The  pecu- 
liar division  of  certain  annelids  has  been  already  mentioned. 
The  budding  zone  is  formed,  and  produces  a  new  head  and  a 
new  tail.  In  a  parasitic  tapeworm  we  have  discovered  a 
vesicular  stage  in  the  life  cycle.  At  certain  spots  upon  the 
wall  of  the  vesicle  arise  new  heads,  each  of  which  initiates  the 
formation  of  a  new  tapeworm.  Specially  interesting  are  the 
cases  of  precocious  division,  which  we  have  learned  about 
recently,  and  in  which  we  encounter  the  division  of  an  egg 
before  the  embryo  proper  has  developed.  Thus  Kleinenberg16 
observed  in  certain  earthworms  that  two  individuals  develop 
regularly  from  one  egg,  an  observation  which  has  been  con- 
firmed by  the  American  investigator,  E.  B.  Wilson.17  Still 
more  remarkable  are  the  occurrences  in  certain  parasitic 
hymenoptera,  in  which  not  merely  two  but  many  individuals 


46  THE   DOCTRINE    OF    IMMORTALITY 

are  created  from  a  single  egg.  This  phenomenon  is  termed 
polyembryony.  It  was  surprising  to  discover  recently  that 
polyembryony  occurs  in  a  mammal.  In  the  year  1885  Von 
Jhering  observed  that  the  armadillo  regularly  produces  four 
embryos  in  one  sac,  and  he  expressed  the  supposition  that  they 
arise  from  a  single  ovum.  Professor  Patterson18  of  the  Uni- 
versity of  Texas  has  studied  the  phenomenon  carefully  in  a 
species  which  occurs  in  Texas.  The  development  of  ordinary 
mammals  begins  with  the  formation  of  a  small  vesicle.  At 
one  pole  of  this  vesicle  there  accumulate  a  small  number  of  cells 
in  which  no  differentiation  is  recognizable.  The  accumula- 
tion is  termed  the  germinal  disc  and  produces  the  embryo. 
Patterson  obtained  eggs  of  the  armadillo  in- the  vesicular  stage, 
and  found  upon  each  vesicle  four  distinct  germs  discs.  Each 
disc  forms  an  embryo.  Thus  it  becomes  certain  that  in  this 
mammal  four  embryos,  always  of  the  same  sex,  arise  from 
one  ovum. 

It  is  also  possible  to  cause  artificial  polyembryony  with 
certain  eggs.  When  an  egg  begins  its  development,  it  divides 
and  when  the  egg  is  small  the  division  usually  produces  two 
cells  alike  in  size.  Driesch19  was  the  first  to  make  the  interest- 
ing experiment  so  to  shake  an  egg  in  the  two-called  stage 
that  the  two  cells  were  separated  from  one  another.  Under 
favorable  conditions  each  of  the  separated  cells  forms  an 
embryo.  The  original  experiment  was  made  with  the  eggs  of 
sea  urchins.  The  artificial  polyembryos  do  not  attain  a  nor- 
mal size,  and  therefore  do  not  develop  quite  as  do  the  natural 
embryos.  The  experiments  of  Driesch  have  been  repeated  by 
many  Americans  and  much  extended,  and  indeed  with  such 
eagerness  that  for  a  certain  period  we  ^termed  our  embryolo- 
gists  "  egg  Shakers. "  You  know  probably  that  the  Shakers  are 
a  Quaker  sect,  dedicated  to  celibacy. 


THE    DOCTRINE    OF    IMMORTALITY  47 

A  special  form  of  division  is  budding,  which  plays  an  im- 
portant role,  especially  among  the  hydroids.  The  process  is 
described  in  all  text-books,  and  need  therefore  be  mentioned 
merely.  A  little  superficial  group  of  cells  begins  to  grow  and 
forms  finally  a  new  polyp. 

In  the  cases  considered  thus  far,  a  number  of  cells  partici- 
pate in  the  propagation.  In  the  case  of  the  so-called  partheno- 
genesis the  creation  of  a  new  individual  starts  from  a  single 
cell.  This  cell  is  an  egg,  which  develops  without  being  fer- 
tilized. Great  interest  was  excited  by  the  discovery  of  artifi- 
cial parthenogenesis  by  A.  C.  Mead.20  In  the  artificial  devel- 
opment we  utilize  chemical  action  which  replaces  fertiliza- 
tion proper,  and  so  excites  the  ovum  that  it  develops  further. 

In  all  these  cases  the  propagation  is  effected  by  the  separa- 
tion of  living  material  from  the  body  of  a  living  individual. 
The  separated  substance  remains  continuously  alive.  The 
substance  may  be  comprised  of  many,  several,  or  only  one 
cell.  The  number  of  cells  is  unessential;  essential  is  only 
that  the  substance  is  alive  and  remains  alive. 

The  separated  substance  inherits  the  primitive  organiza- 
tion, or,  more  exactly  expressed,  has  the  parental  organiza- 
tion, because  it  is  unaltered  parental  substance.  We  come 
up  against  a  question  which  we  unfortunately  cannot  yet 
answer :  How  is  the  organization  regulated  ?  It  seems  a  matter 
of  indifference  how  the  asexual  propagation  is  accomplished. 
Each  time  the  development  proceeds,  until  the  original 
organization  is  completed.  When  the  budding  zone  of  anne- 
lids forms  a  new  tail  in  the  anterior  part  of  the  animal  and  a 
new  head  for  the  posterior  part,  we  can  only  say  that  a  regula- 
tion of  the  organization  is  shown.  There  is  no  means  for 
determining  more  exactly  the  process.  It  seems  to  be  clear  that 
this  regulation  is  not  to  be  sought  only  in  the  developing  cells 


48  THE    DOCTRINE    OF    IMMORTALITY 

themselves  but  also  in  part  at  least  in  an  influence  exerted  by 
the  rest  of  the  body.  In  the  case  of  polyembryony,  the  rudi- 
ment, or  anlage,  possesses  the  capacity  of  forming  all  tissues 
and  organs.  During  regeneration  also,  which  in  many  animals 
may  go  very  far,  we  see  that  the  complete  structure  is  produced 
anew  and  we  recognize  here  again  the  phenomenon  which  we 
call  regulation.  The  physiological  explanation  of  regulation 
we  do  not  yet  possess,  although  we  have  learned  already  a 
little  concerning  it. 

The  sexual  propagation  plays  a  greater  role  than  the 
asexual,  and  is  often  the  exclusive  method  of  progagation, 
especially  in  the  higher  plants  and  animals.  We  learned  in 
yesterday's  lecture  that  the  cells  of  the  animal  body  dif- 
ferentiate themselves,  that  is  to  say,  that  their  protoplasm 
acquires  new  qualities  and  that  their  power  of  division 
diminishes.  Differentiated  cells  are  not  suited  for  propaga- 
tion. If  it  should  occur  that  all  the  cells  of  an  animal  or  a 
plant  should  pass  through  a  complete  cytomorphosis,  they 
would  all  die  off,  the  organism  would  reach  its  end,  and  could 
produce  no  progeny.  As  a  matter  of  fact,  however,  all  the 
cells  do  not  become  differentiated.  Of  the  undifferentiated 
cells,  the  necessary  number  in  each  species  is  reserved  for 
the  formation  of  the  sexual  cells.  In  phanerogams  we  find 
undifferentiated  cells  in  the  buds.  When  the  bud  forms  a 
flower  and  sexual  cells  are  developed  in  connection  with  it, 
we  learn  that  some  of  these  undifferentiated  cells  are  made 
use  of.  It  is  entirely  unknown  to  us  how  the  transformation 
of  undifferentiated  cells  into  sexual  cells  is  caused.  We  can 
observe  with  the  microscope  alterations  in  the  structures  of 
the  cells,  but  the  cause  of  these  alterations  remains  hidden 
from  us.  In  lower  animals  we  find  relations  which  to  a 
certain  extent  resemble  those  prevailing  in  the  phanerogams, 


THE   DOCTRINE    OF   IMMORTALITY 


49 


since  in  them  also  there  occur  slightly  differentiated  cells 
which  are  applied  for  the  formation  of  sexual  cells.  The 
other  cells,  which  constitute  by  far  the  majority,  we  name 
the  somatic  cells,  and  therefore  say  that  every  animal  body 
consists  of  many  somatic  and  a  few  sexual  cells.  It  we  pass 
from  the  lower  to  the  higher  animals,  we  find  that  the  separa- 


Germ-CellG 


FIG.  23. — Section  through  the  posterior  part  of  an  embryo  of  the  dog-fish,  Squalus 
acanthias.  Germ  cells  designates  the  group  of  sexual  cells  which  have  united  in  one 
group,  which  still  lies  far  from  the  position  of  the  future  sexual  gland.  Ect,  ectoderm ; 
Md,  spinal  cord;  Nch,  axis  of  the  body  (notochord);  Mes,  mesoderm;  Ent,  entoderm; 
Yolk,  yolk-mass. 

tion  of  the  two  classes  of  cells,  the  names  of  which  we  have 
just  heard,  becomes  sharper.  We  have  succeeded  recently  in 
observing  the  precocious  separation,  or  isolation,  of  the  sex 
cells  in  vertebrates.  Their  number  is  very  small  in  propor- 
tion to  the  number  of  somatic  cells.  In  the  young  embryo 


5o 


THE   DOCTRINE    OF    IMMORTALITY 


of  the  dog-fish  there  lies  at  either  side  in  the  neighborhood  of 
the  developing  intestinal  canala  group  of  cells,  Fig.  23,  germ 

Chrysemys 


Arch 


FIG.  24. 


cells,  which  resemble  one  another  closely,  and  which  may  be 
easily  distinguished  from  the  other  cells  of  the  body.     They 


THE   DOCTRINE    OF   IMMORTALITY 


Lepidosteus 


Lepidosteus 


Roof  End. 
Sub- germ  Cav 

Sub-cerm.  End., 


\Periph.  End.  \Vit  End. 

FIG.  24. — Diagrams  to  show  the  migration  of  sexual  cells  in  four  different  verte- 
brates. Arch,  primitive  intestine  (archenteron) ;  Int,  intestine;  Lat.  Mes,  lateral 
mesoderm;  Mes,  mesothelium,  or  wall  of  the  body  cavity;  Meson,  embryonic  kidney 
(mesonephros);  Myo,  anlage  of  the  muscle  (myotome);  Noto,  primitive  axis  (noto- 
chord);  S.C,  sexual  cells  in  migration;  W.D,  renal,  or  Wolffian  duct. — After  Bennett 
M.  Allen. 


52  THE   DOCTRINE    OF   IMMORTALITY 

are  the  sexual  cells  and  they  accomplish  during  the  later 
development  a  wonderful  migration,  for  they  move  through 
the  wall  of  the  digestive  canal  and  then  through  the  mesen- 
tery until  they  reach  the  spot  where  the  sexual  gland  arises. 
We  known  this  interesting  history  through  the  investigations 
of  F.  A.  Woods,21  which  were  made  in  my  laboratory.  For- 
merly one  assumed  that  the  sexual  cells  arose  in  the  gland, 
but  this  is  probably  not  the  case  in  any  vertebrate.  Another 
American,  B.  M.  Allen,22  has  greatly  enlarged  our  knowledge 
of  the  history  of  the  sex  cells  in  vertebrates.  By  the  re- 
searches of  this  investigator,  we  now  know  that  also  in  the 
turtle,  the  frog,  and  in  two  fishes,  Amia  and  Lepidosteus,  the 
sexual  cells  may  be  recognized  very  early.  They  lie  at 
first  far  from  the  sexual  gland  into  which  they  later  migrate. 
The  paths  which  these  cells  take  during  their  migration 
differ  for  the  species  mentioned,  Fig.  24.  Several  European 
investigators  have  also  occupied  themselves  with  the  history 
of  the  sexual  cells  in  vertebrates.  In  spite  of  the  fact  that 
much  remains  to  be  cleared  up,  we  may  nevertheless  assert 
that  vertebrates  have  special  germinal  paths,  as  they  are 
called.  In  other  words  sexual  cells  are  held  apart.  They  pass 
through  their  development  by  themselves  and  have  nothing 
in  common  with  the  somatic  cells.  They  do  not  participate 
in  the  structure  of  the  body,  but  remain  almost  like  guests 
which  are  cared  for  by  the  other  cells.  When  the  proper 
time  comes  the  sexual  cells  change  themselves,  as  the  case 
may  be,  into  male  or  female  elements.  Since  we  know  the 
history  of  these  cells  exactly  in  several  cases,  we  are  able  to 
assert  that  in  sexual  as  in  asexual  propagation  the  living 
substance  continues  uninterruptedly.  This  continuation  up 
to  the  origin  of  the  sexual  elements  we  have  actually  ob- 
served. 


THE   DOCTRINE    OF    IMMORTALITY 


53 


In  insects  also  a  special  germinal  path  has  been  discovered. 
The  small  egg  of  these  animals  is  usually  oval  in  form.  The 
French  anatomist,  Charles  Robin,  reported  in  1862  that  a 
special  group  of  cells  appears  soon  after  the  conclusion  of  the 
segmentation  of  the  ovum.  Balbiani  showed  twenty  years 
later  that  these  pole  cells,  which  are  not  to  be  confused  with 
the  so-called  polar  globules  or  directive  corpuscles,  afterward 


Bl, 


FIG.  25. — Preparations  from  the  egg  of  a  beetle,  Leptinotarsa.  A,  the  whole 
egg  after  completion  of  segmentation,  at  the  posterior  end  one  sees  the  accumulation 
of  the  superficial  sexual  cells,  p.z,  Xso;  B,  two  cells,  X85o;  bl.c,  ordinary  somatic  or 
blastodermiccell;  p.c,  sexual  cell  (pole  cell).  C,  section  through  an  egg,  Xio5',Bl, 
blastodermic  layer  of  somatic  cells;  p.c,  sexual  cells  which  migrate  into  the  interior 
of  the  egg,  in  order  to  enter  the  sexual  gland  proper. — After  R.  W .  Hegner. 

pass  into  the  sexual  gland.  The  investigation  of  R.  W.  Heg- 
ner23 of  Wisconsin  University  offers  us  the  most  exact  account 
of  the  history  of  these  cells  which  we  possess  as  yet.  From 
his  paper  the  pictures  in  Fig.  25  have  been  taken.  The  pole 
cells  of  Robin  are  sexual  cells  which  separate  precociously 
from  the  somatic  cells,  and  after  they  have  completed  their 
migration,  change  in  the  sexual  gland  into  sexual  elements. 
We  know  for  animals  as  for  plants  a  physiological  cause 


54  THE   DOCTRINE    OF   IMMORTALITY 

for  the  remarkable  alterations  which  produce  from  a  sexual 
cell,  as  the  case  may  be,  an  ovum  or  a  spermatozoon.  In 
the  fifth  lecture  we  shall  return  to  the  consideration  of  the 
visible  alterations  during  this  transformation. 

Let  us  now  assume  that  we  have  eggs  and  spermatozoa, 
and  occupy  ourselves  with  their  further  history.  Science  has 
acquired  correct  notions  of '  these  elements  very  gradually. 
A  hundred  years  have  not  yet  passed  since  the  publication  of 
the  discovery  of  the  eggs  of  mammals  by  Carl  Ernst  von  Baer. 
Eighty  years  ago  one  considered  the  spermatozoa  as  parasites, 
although  they  had  been  known  since  1628.  The  investiga- 
tions of  Koelliker  first  demonstrated  the  true  significance  of 
spermatoza.  That  the  semen  acted  to  fertilize  ova  has  been 
long  known,  but  so  long  as  one  did  not  know  the  male  and 
female  sexual  elements  of  the  higher  animals  one  could  have 
no  clear  conception  of  reproduction.  During  the  period  of 
ignorance  all  sorts  of  wonderful  theories  arose,  which,  how- 
ever, had  no  value  because  precisely  that  which  they  should 
explain  was,  in  its  essentials,  unknown.  We  must  express  a 
warning  against  theories  of  this  sort,  because  even  to-day  we 
are  much  inclined  to  make  up  for  lacking  knowledge  by 
theories.  It  was  not  until  the  seventies  of  the  previous 
century  that  it  became  possible  to  understand  the  role  of 
sexual  elements  in  reproduction  through  the  epoch-making 
investigations  of  the  gifted  Oskar  Hertwig.  Hertwig  was  at 
that  time  Privatdozent  in  Jena,  and  I  rejoice  that  it  is 
permitted  me  to  express  here  the  admiration  which  all  biolo- 
gists bestowed  on  his  discovery.  Hertwig  showed  that 
fertilization  consists  essentially  in  the  union  of  one  spermato- 
zoon with  one  ovum.  Since  the  ovum  is  very  large  in  pro- 
portion to  the  male  element  we  are  accustomed  to  describe 
this  union  as  the  penetration  of  the  spermatozoon  into  the 


THE   DOCTRINE    OF   IMMORTALITY  55 

ovum.  Her  twig  investigated  various  species  of  eggs  and 
observed  the  same  fundamental  phenomena  in  them  all. 
Out  of  the  head  of  the  entering  spermatozoon  there  arises  a 
nucleus-like  structure  or  pronucleus.  Before  or  during 
impregnation  the  nucleus  of  the  ovum  loses  a  portion  of  its 
contents  by  a  process  which  we  call  the  phenomenon  of 
maturation.  The  part  of  the  nucleus  of  the  ovum  which 
remains  forms  the  female  pronucleus.  The  two  pronuclei 
unite  and  form  a  new  complete  nucleus.  The  fertilization 
is  now  accomplished,  and  further  development  begins.  The 
fertilized  ovum  divides,  and  so  does  also  the  so-called  segmen- 
tation nucleus,  which  owes  its  origin  to  the  fusion  of  the  two 
pronuclei.  We  see  therefore  that  substances  from  the  mater- 
nal side  and  from  the  paternal  side  are  employed  for  the  act 
of  propagation.  A  new  individual  obtains  its  life  from  both 
parents.  In  this  case  also  the  history  is  uninterrupted. 

W.  H.  Moenkhaus,25  Professor  in  the  University  of 
Indiana,  has  furnished  us  the  most  brilliant  proof  of  the 
accuracy  of  the  assertion  just  made.  He  reared  the  hybrids 
of  two  fishes,  Menidia  and  Fundulus.  The  chromosomes  of 
Menidiaare  noticeably  smaller  than  those  of  Fundulus.  In 
the  hybrids  Moenkhaus  discovered  both  forms  of  chromo- 
somes appearing  clearly  at  the  time  of  cell  division.  This 
extremely  interesting  case  teaches  us  by  direct  observation 
that  living  substance  from  both  parents  propagates  itself  in 
the  progeny  in  visible  form. 

At  the  beginning  of  today's  lecture  we  cited  the  Latin 
saying  " omne  vivum  ex  vivo."  It  required  the  prolonged 
researches  of  many  investigators  to  reveal  to  us  the  ways 
which  living  substance  adopts  in  order  to  continue  without  a 
break.  The  relations  may  be  easily  recognized  in  asexual 
reproduction,  but  in  the  case  of  sexual  reproduction  we  must 


56  THE   DOCTRINE    OF    IMMORTALITY 

ascertain  the  history  of  the  sexual  cells,  the  occurrence  of 
sexual  elements  in  all  animals,  and  the  internal  processes 
during  fertilization,  in  order  to  establish  the  necessary  founda- 
tion for  the  modern  doctrine  of  immortality.  From  the 
numerous  researches  made,  we  draw  the  safe  conclusion  that 
living  beings  consist  of  protoplasm  and  nucleus  which  have 
arisen  from  earlier  living  protoplasm  and  earlier  living  nuclei. 
The  animals  and  plants  of  today  exist  only  because  protoplasm 
in  itself  is  immortal.  Only  when  protoplasm  changes  itself 
or  is  destroyed  by  external  influences  does  it  die.  To  us  the 
verse  "omne  vivum  ex  vivo"  means  the  immortality  of 
protoplasm. 

This  fact  procures  us  a  better  insight  into  heredity.  It  is 
well  known  to  us  all  that  every  living  species  maintains 
itself  with  slight  alteration.  This  phenomenon  signifies  to 
us  that  protoplasm  possesses  the  capacity,  when  supplied 
with  food  material,  to  produce  more  protoplasm  of  the  same 
constitution  as  itself.  We  can  offer  no  further  explanation 
of  this  wonderful  capacity.  For  us  it  is  merely  a  fact  which; 
however,  offers  us  a  theory  of  heredity,  namely  that  the 
progeny  are  similar  to  their  parents  because  they  are  developed 
from  the  same  protoplasm.  The  creation  of  a  new  generation 
appears  to  us  merely  as  the  continuation  of  the  activity  and 
growth  of  the  previous  generations. 

There  has  been  no  lack  of  theories  of  heredity.  The  best 
of  the  older  theories  in  my  opinion  is  that  of  Darwin,  which 
he  termed  "pangenesis."  He  assumed  that  the  cells  give 
off  little  granules  or  atoms  which  circulate  freely  through 
the  whole  body  and  which,  when  they  are  supplied  with  the 
proper  nutrition,  multiply  themselves  by  division  and  then 
may  later  develop  into  cells.  Darwin  for  the  sake  of 
clearness  has  named  these  granules  "cell  gemmules,"  or 


THE   DOCTRINE    OF    IMMORTALITY  57 

simply  "gemmules."  He  assumed  that  they  pass  over 
from  the  parents  to  the  descendants,  and  usually  develop 
themselves  in  the  first  generation.  Darwin's  pangenesis 
explains  heredity.  It  is  the  hypothesis  of  a  master,  and  as  a 
succinct  and  comprehensive  explanation  of  the  facts  of  heredity 
must  always  command  admiration.  Since  Darwin's  time 
many  modifications  of  the  doctrine  of  pangenesis  have  been 
proposed.  These  modifications,  however,  possess  for  us 
merely  historical  interest,  for  with  the  progress  of  science  they 
have  become  superfluous. 

The  new  doctrine  of  heredity  is  due  to  Professor  Moritz 
Nussbaum,  who  laid  special  stress  upon  the  discovery  of 
the  germinal  paths  in  animals,  for  he  recognized  in  these  an 
arrangement  to  separate  special  germinal  cells  from  the 
somatic  cells.  He  concluded  that  a  portion  of  the  germ-plasm 
is  withheld  from  the  developing  ovum,  kept  comparatively 
unaltered,  and  employed  for  the  formation  of  sexual  elements, 
so  as  to  become  directly  the  germ-plasm  of  a  new  generation. 
It  is  clearly  superfluous  to  still  employ  the  expression  germ- 
plasm  which  corresponds  to  speculative  needs,  and  which  we 
may  now  leave  out  of  consideration.  It  is  simpler  to  speak 
merely  of  living  substance.  Nussbaum's  theory  has  in  the 
course  of  time  become,  strictly  speaking,  the  only  theory  of 
heredity  which  we  value. 

If  the  time  at  our  disposal  permitted,  it  would  be  interesting 
to  analyze  carefully  some  of  the  theories  of  heredity  which 
have  arisen  in  association  with  Nussbaum's  doctrine.  The 
majority  of  these  theories  search  for  a  special  germ-plasm,  to 
use  Weissmann's  expression.  Nageli  speaks  of  idioplasm. 
Some  authorities  have  sought  to  bring  heredity  into  relation 
with  visible  parts  of  the  protoplasm  or  of  the  nucleus.  Oskar 
Hertwig  was  the  first  to  interpret  the  nucleus  as  the  organ  of 


58  THE   DOCTRINE    OF   IMMORTALITY 

heredity,  a  view  which  many  eminent  investigators  have 
since  defended.  We  must  today  admit  that  the  nucleus  plays 
a  part  in  heredity,  but  not  an  exclusive  role.  The  investiga- 
tions of  two  Americans,  Conklin26  and  Lillie,27  furnish  the 
proof  that  in  certain  cases  distinct  regions  can  be  distin- 
guished in  the  protoplasm  of  the  undeveloped  ovum.  When 
the  development  proceeds  each  of  these  regions  plays  a  special 
role  in  the  formation  of  the  body.  It  is  possible  to  alter  the 
normal  distribution  of  the  substances,  which  are  character- 
istic for  the  regions,  without  killing  the  ovum.  This  is 
accomplished  by  the  centrifuge.  Conklin  has  succeeded  in 
observing  in  centrifuged  eggs  that  the  substances,  which  have 
acquired  a  new  position  in  the  ovum,  nevertheless  form  the 
same  structures  as  before.  From  these  observations  he  draws 
the  just  conclusion  that  organ-forming  substances  are  present 
in  these  ova  from  the  beginning.  That  which  arises  in  the 
course  of  the  development  of  the  new  individual  is,  in  these 
cases,  certainly  determined  at  least  in  part  by  the  protoplasm 
of  the  ovum.  Hence  we  must  admit  that  the  protoplasm  also 
participates  in  heredity.  I  do  not  see  how  we  can  accept 
the  theory  that  the  nucleus  is  exclusively  the  organ  of  heredity. 
On  the  contrary  we  must  say  that  the  essence  of  reproduction 
is  the  continuation  of  the  growth  of  immortal  protoplasm. 
The  history  of  protoplasm  is  uninterrupted,  and  therefore  we 
say :  the  immortality  of  the  protoplasm  and  of  the  nucleus  is 
also  the  explanation  of  heredity. 


IV. 
THE  EVOLUTION  OF  DEATH. 

Mortality  was  formerly  regarded  as  the  necessary  end- 
phenomenon  of  life.  It  was  not  until  our  own  times  that 
it  appeared  probable  to  us  that  so-called  natural  death  does 
not  occur  with  all  organisms. 

The  development  of  the  higher  plants  and  animals  begins 
with  the  fertilized  ovum.  By  continued  division  such  an  egg 
produces  the  cells  which  form  the  plant  or  animal,  as  the  case 
may  be.  Many  years  ago  Huxley  defended  the  thesis  that 
all  cells  which  arise  from  a  single  ovum  belong  together  and 
constitute  a  cycle.  He  further  proposed  to  regard  all  the 
cells  of  a  single  cycle  as  constituting  the  individual  proper. 
The  problem  of  individuality,  however,  which  formerly 
often  occupied  thinkers,  has  lost  much  in  interest  and  signifi- 
cance, owing  to  the  progress  of  biology.  In  the  higher  animals 
as  in  the  unicellular,  we  encounter  real  individuals  ,  but  in  the 
lower  multi cellular  animals  we  recognize  on  the  contrary  no  dis- 
tinct individualities.  Thus,  for  example,  in  the  case  of  corals 
and  sponges,  we  cannot  speak  of  individuals.  Under  these 
conditions  Huxley's  conception  of  the  cycle  was  very  seduc- 
tive to  biologists.  It  could  apparently  be  very  well  applied 
to  the  unicellular  organisms  because  in  many  of  them  con- 
jugation had  been  observed.  Conjugation  is  a  phenomenon 
closely  related  with  sexual  reproduction.  It  was  assumed 
that  conjugation  served  to  excite  the  cell  division  of  unicellu- 
lar organisms.  If  conjugation  and  the  fertilization  of  the  ovum 
are  homologous  phenomena,  then  we  are  justified  in  regard- 
s' 


60  THE    EVOLUTION    OF-BEATH 

ing  in  both  cases  the  exciting  of  cell  division  as  the  immediate 
consequence  alike  of  conjugation  and  fertilization.  In  both 
cases  there  would  arise  homologous  cycles  of  cell  generations. 
Thus  we  should  have  to  deal  in  both  types  of  organisms  with 
individuals  in  Huxley's  sense.  The  only  difference  between 
the  two  types,  which  from  our  present  point  of  view  must  be 
regarded  as  important,  is  that  the  cells  in  the  lower  type  sepa- 
rate from  one  another,  while  in  the  higher,  on  the  contrary, 
they  unite  to  form  a  plant  or  animal.  Death,  as  we  ordinarily 
observe  it,  is  the  breakdown  of  a  multicellular  organism,  and 
natural  death  is  a  consequence  of  old  age.  This  considera- 
tion leads  us  directly  to  the  question:  Do  old  age  and  natural 
death  occur  in  unicellular  organisms?  Weissmann,  who  has 
written  several  times  concerning  death,  has  not  conceived 
the  problem  rightly,  so  that  his  discussions  of  death  go 
astray  in  several  essential  respects. 

The  first  serious  experiments  to  determine  by  direct  ob- 
servation whether  old  age  occurs  in  unicellular  animals  were 
carried  out  by  the  French  investigator,  Maupas.28  " He 
reared  Protozoa  through  many  generations.  Of  each  genera- 
tion he  took  a  few  individuals,  allowed  them  to  propagate 
themselves  and  noted  the  rapidity  with  which  the  divisions 
followed  upon  one  another.  He  found  that  the  rapidity 
diminished  until  a  new  conjugation  occurred,  whereupon  the 
animals  recovered.  Later  tests  of  these  results  have  shown 
that  the  experiments  of  Maupas  were  open  to  criticism,  in 
part  because  at  that  time  the  great  influence  of  external  con- 
ditions upon  Infusoria  was  unknown,  so  that  the  possibility 
remains  that  the  retardation  of  the  division  he  observed  was 
conditioned  not  by  internal  but  by  external  causes.  Further, 
in  order  to  bring  about  conjugation,  he  introduced  into  his  cul- 
tures newly  captured,  wild  individuals.  His  cultures,  there- 


THE   EVOLUTION    OF   DEATH  6 1 

fore,  were  not  kept  strictly  pure.  In  America  a  long  series  of 
researches  on  the  rapidity  of  division  in  Protozoa  has  been 
made,  largely  upon  the  instigation  of  G.  N.  Calkins,29  who 
discovered  that  Infusoria  may  suffer  "depression"  a  result 
which  has  been  confirmed  by  further  investigations  of  his  own, 
of  his  pupils,  and  of  other  American  investigators.  The  de- 
pression arises  gradually,  the  animals  become  inert,  nourish 
themselves  poorly,  and  divide  slowly  or  even  not  at  all.  If 
the  depression  lasts  too  long  the  animals  may  die  off  Calkins 
considered  the  depression"  to  be  senescence,  or  a  growing 
old.  (He  has  since  himself  questioned  the  justness  of  this 
interpretation.) 

Our  conception  of  senescence  is  based  on  the  observation 
of  the  higher  animals  and  plants,  and  comprises  not  merely 
the  increasing  weakness,  but  also  alterations  in  structure 
which  go  far  and  are  very  striking.  The  Infusoria  during 
their  depression  show  no  corresponding  alterations  of  their 
organization;  hence  in  my  belief  we  cannot  homologize  this 
phenomenon  in  the  Protozoa  with  the  senescence  of  higher 
animals.  In  this  belief  we  are  confirmed  by  the  fact  that  the 
newer  investigations  of  conjugation  make  it  improbable  that 
it  serves  to  renew  and  hasten  the  growth  and  division  of 
unicellular  organisms.  Indeed,  it  is  possible  that  conjuga- 
tion does  not  have  this  function  at  all.  Significant  here  are 
the  studies  of  the  very  talented  investigator,  H.  S.  Jennings,30 
which  demonstrate  that  conjugation  serves  to  increase  varia- 
bility. Jennings  observed  that  Paramaecium  exhibit  consid- 
erable variability.  During  ordinary  division  the  individuals 
remain  more  alike,  but  after  conjugation  their  variation  in- 
creases. His  careful  statistics  leave  no  doubt  as  to  his  results. 
It  is  probable  that  sexual  reproduction  also  has  the  purpose 
of  maintaining  the  variability  of  the  forms.  The  interperta- 


62  THE    EVOLUTION    OF   DEATH 

tion  that  impregnation  has  the  purpose  of  increasing  varia- 
bility in  order  to  offer  room  for  the  play  of  natural  selection 
originated  with  Weissmann.  (It  is  said  that  Treviranus  had 
previously  expressed  this  view,  but  I  have  as  yet  been  unable  to 
personally  confirm  this  statement.)  Impregnation  has  also 
certainly  to  care  both  for  heredity  and  for  the  initiation 
of  further  development.  We  know  now  that  these  functions 
may  be  separated  experimentally.  If  sexual  reproduction  be 
conceived  as  a  modification  of  conjugation,  then  we  may  assume 
that  the  function  of  initiating  development  was  acquired  later. 
Returning  to  the  Infusoria  we  encounter  in  them,  so  far  as  the 
available  observations  go,  a  so-called  depression  indeed,  but 
no  senescence  in  the  strict  sense.  (Quite  conclusive  as  to 
the  absence  of  senescence  are  the  experiments  of  L.  L.  Wood- 
ruff,* who  has  maintained  a  pedigreed  race  of  Paramecium 
for  five  years  without  conjugation.  If  all  the  possible  indi- 
viduals had  survived,  they  would  have  made  a  volume  of 
protoplasm  many  million  times  the  volume  of  the  earth). 
Calkins,  as  said  above,  originally  interpreted  depression 
as  a  true  senescence  and  declared  the  diminution  of  metab- 
olism to  be  the  essential  characteristic  of  old  age.  This  view 
has  been  adopted  by  C.  M.  Child31  and  E.  G.  Conklin.32  Pro- 
fessor Child  has  made  experiments  with  a  simple  worm,  Plana- 
ria.  He  treated  these  animals  with  alcohol  by  placing  them 
in  water  to  which  i  per  cent,  of  alcohol  had  been  added. 
The  results  he  obtained  are  interesting  and  valuable.  He 
seems  to  me,  however,  to  go  too  far  when  he  asserts  that  if 
the  metabolism  diminishes  the  animals  become  old.  It  is 
true  that  in  the  higher  animals,  when  they  become  old,  met- 

*  L.  L.  Woodruff:  Biologisches  Centralblatt,  XXXIII,  p.  34,  1913.  Professor 
Woodruff  has  informed  me  that  on  April  3,  1913,  he  had  the  36501!!  generation  of 
the  mentioned  Paramecium  colony. 


THE   EVOLUTION    OF   DEATH  63 

abolism  becomes  slower,  but  certainly  one  cannot  therefore 
assert  that  every  lessening  of  the  metabolism  implies  a  becom- 
ing old.  According  to  the  sum  total  of  our  knowledge  we 
must  regard  organization  as  the  cause  of  function.  This  is 
the  only  interpretation  which  a  physiologist  may  admit. 
When  therefore  an  organization  is  so  altered  that  the  metabo- 
lism diminishes,  this  diminution  has  to  be  considered  a  conse- 
quence and  not  a  cause.  Metabolism,  however,  is  influenced 
by  many  factors,  as  every  practicing  physician  experiences 
daily.  If  we  accept  Child's  opinion  we  are  led  logically  to 
the  conclusion  that  each  one  of  us  may  become  alternately 
young  and  old  according  as  his  metabolism  increases  or 
diminishes.  We  should  have  to  say,  for  example,  that  a 
man  who  performs  strenuous  and  muscular  work  was  reju- 
venated, while  on  the  contrary  one  carrying  on  mental  work, 
during  which  the  metabolism  is  less,  might  become  older.  It 
seems  to  me  clear  that  we  cannot  interpret  the  diminution  of 
the  metabolism  as  a  characteristic  of  age  in  the  sense  of  Cal- 
kins. In  other  words,  we  cannot  view  the  depression  in  proto- 
zoa as  senescence.  Thus  we  reach  the  conclusion  that  natural 
death,  so  far  as  we  know  at  present,  does  not  occur  in  unicellu- 
lar organisms,  and  as  a  consequence  of  this  we  mention  the 
corollary  that  natural  death  first  appeared  in  the  world  as  the 
higher  multicellular  plants  and  animals  were  evolved. 

We  pass  now  to  the  examination  of  senescence  in  the 
higher  animals,  a  theme  which  has  claimed  my  active  interest 
for  many  years.  If  we  consider  the  phenomena  as  they  are ./ 
known  to  us  all,  we  recognize  at  once  that  a  diminution  of  the 
rapidity  of  growth  is  characteristic  of  age,  and  thus  we  are 
induced  to  investigate  growth.  Obviously  we  must  determine 
how  the  rapidity  of  growth  alters  with  advancing  age.  For 
such  an  investigation  it  is  important  to  exclude  the  influence 


64 


THE   EVOLUTION    OF_J1EATH 


of  temperature,  which  is  known  to  have  a  great  influence  upon 
growth.  Nature  makes  this  exclusion  for  us  in  the  case  of 
warm-blooded  animals.  I  selected  for  my  own  experiments  on 
warm-blooded  animals  guinea  pigs  for  various  practical  reason 
and  I  maintained  a  colony  of  these  animals  for  many  years. 
Every  animal  of  the  colony  was  weighed  at  definite  intervals  of 
age.  After  many  thousands  of  determinations  of  the  weight 


~JfLSi{Jvir( 


wnj/i 
1fff 


50- 


FIG.  26. — Graphic  representation  of  the  increase  of  weight  in  children  of  the  Boston 

schools.— After  H.  P.  Bowditch. 
(Knaben,  boys.     Madchen,  girls.     Jahre,  years.) 

had  been  collected,  they  were  worked  over  statistically.33 
My  first  problem  was  to  invent  a  method  which  permitted 
the  representation  of  the  rate  of  growth.  Formerly  investi- 
gators were  satisfied  to  represent  growth  graphically  in  a  very 
simple  way.  Curves  were  constructed  in  which  the  abscissae 
corresponded  to  the  age,  and  the  ordinates  to  the  weight, 
Fig.  26.  Such  a  curve,  however,  although  it  represents  the 


THE    EVOLUTION    OF   DEATH  65 

increase  of  weight,  does  not  show  the  rate  of  growth.  The 
real  rate  can  be  represented  in  the  following  manner  with 
approximate  accuracy.  From  the  weight  which  an  animal 
has  on  a  given  day  and  that  which  is  found  at  the  next  weigh- 
ing, I  reckoned  the  average  daily  increase  during  the  period 
between  the  two  weighings,  and  then  changed  these  increases 
into  the  per  cent,  value  of  the  weight  at  the  beginning  of  the 
period.  This  method  may  be  modified  by  calculating  instead 
of  the  daily,  the  monthly  or  yearly  percentage  increases. 


51117232935   ^5      60     75     90     105    120    135    150    165    180    195    210  days 
FIG.  27. — Curve  of  the  daily  percentage  increase  in  weight  of  male  guinea-pigs. 

The  method  is  of  course  mathematically  not  exact,  since  the 
weight  is  constantly  changing.  It  suffices,  however,  for  our 
purposes.  It  is  easy  after  one  has  calculated  a  series  of  per- 
centage increments  in  weight  to  construct  a  curve.  The 
results  obtained  in  this  way  I  wish  to  lay  before  you.  When 
guinea-pigs  are  born,  they  suffer  in  consequence  of  the  great 
sudden  disturbance  of  their  conditions  of  living  a  temporary 
inhibition  of  their  development.  They  recover  within  two 
or  three  days,  and  thereupon  we  observe  that  they  may 
increase  their  weight  over  5  per  cent,  in  one  day,  Fig.  27. 


66 


THE   EVOLUTION   OF  DEATH 


By  the  time  they  are  seventeen  days  old,  they  grow  only 
only  about  4  per  cent,  and  at  forty-five  days  only  a  little 
more  than  i  per  cent,  and  from  this  age  on  the  rate  of  growth 
sinks  slowly  until  at  the  end  of  the  first  year  it  becomes 
almost  zero.  The  general  process  is  the  same  in  females, 
Fig.  28,  as  in  males,  although  certain  inequalities  occur. 
It  is  obvious  that  if  we  consider  the  curves,  Figs.  27  and  28, 
carefully,  we  can  distinguish  in  them  two  chief  periods,  which, 
however,  pass  into  one  another  without  definite  boundaries. 


5 Tl  17 23 2933    tf      60      75      90     105    120    135    150    165    180    195    210  days 
FIG.  28. — Curve  of  the  daily  percentage  increase  in  weight  in  female  guinea-pigs. 

In  the  first,  shorter  period,  the  rate  diminishes  rapidly.  This 
period  lasts  about  one  and  a  half  months.  The  second  period 
exhibits  a  much  slower  decrease  and  lasts  perhaps  ten  months. 
The  result  was  unexpected.  If  we  accept  the  rate  of  growth 
as  the  measure  of  senescence,  we  must  say  that  young  animals 
grow  old  enormously  faster  than  old  animals.  Since  alter- 
ations in  the  rate  of  growth  of  guinea-pigs  progress  as  de- 
scribed, it  was  to  be  expected  that  in  still  younger  stages  of 
development  the  rate  of  growth  would  be  found  still  greater. 
Now  chickens  when  they  enter  the  world  are  not  so  far 


THE   EVOLUTION   OF   DEATH 


67 


developed  as  guinea-pigs,  and  much  less  far  developed  are 
newborn  rabbits.  I  have  determined  the  rate  of  growth  in 
both  of  these  animals,  and  found  that  chickens,  as  soon  as 


3>2 13  U  33  <t6566677  90  106     130  197  days  3^2 

FIG.  29. — Curve  of  the  daily  percentage  increase  in  weight  in  male  chickens. 


y/i  13  22  33  465666  77  90  106      130  197  days  3« 

FIG.  30. — Curve  of  the  daily  percentage  increase  in  weight  of  female  chickens. 

they  have  recovered  from  their  hatching,  may  grow  as  much  as 
9  per  cent,  per  day,  which  is  much  quicker  than  the  guinea- 
pigs  grow.  The  values  for  the  two  sexes  are  practically  equal, 


68 


THE    EVOLUTION   OF   DEATH 


THE   EVOLUTION    OF   DEATH 


69 


Figs.  29  and  30.  Even  more  striking  is  the  rate  in  rabbits, 
which  immediately  after  birth  may  reach  for  the  males  almost 
1 8  per  cent,  per  day,  and  for  the  females  16  per  cent.,  Fig. 
31,  A  and  B. 

We  encounter  similar  phenomena  in  man,  but  since  man 
grows  much  more  slowly  than  the  three  species  of  animals, 


100% 


20% 
10% 


Years!     2    3    4     5    6     7    8    9    10  11   12  13  14  15  16  17  18  19  20  21  22  23 

FIG.  32. — Curve  of  the  yearly  percentage  increase  in  weight  of  boys. — Reckoned 
from  H.  H.  Donaldson's  table. 


the  growth  of  which  we  have  studied,  I  have  reckoned  the 
increases  as  yearly  percentages,  Fig.  32  represents  the  rate  of 
growth  for  boys,  Fig.  33  for  girls.  The  curves  fall  at  first 
with  great  rapidity,  later  much  more  slowly.  Fig.  34  shows 
the  alterations  in  the  rate  of  growth  in  another  form.  The 
curve  corresponds  to  the  observed  average  weights  in  the  male 


THE   EVOLUTION   OF  DEATH 


200% 


100% 


30% 
20% 
10% 


Years  1 


3456 


8    9    10   11   12  13  H  15  16  17  18  19  20  21  22  23 


FIG    33.  —  Curve  of  the  yearly  percentage  increase  in  weight  of  girls.  —  Reckoned 
from  E.  H.  Donaldson's  table. 


FIG.  34. — Curve  of  human  growth  in  weight,  with  vertical  lines  to  mark  the  dura- 
tion of  loper-cent.  increases. 


THE   EVOLUTION   OF   DEATH 


600% 


sex  up  to  the  age  of  forty  years.  The  vertical  lines  indicate 
by  their  distance  from  one  another  what  interval  is  required  to 
permit  each  time  a  lo-per-cent.  increase  of  the  weight. 

We  may  proceed  further  and  study  growth  during  the 
embryonic  period.  Unfortunately  this  has  not  yet  been  done 
so  thoroughly  and  exactly  as  for  the  development  after  birth. 
Nevertheless  we  can  assert  now  that 
the  growth  of  embryos  proceeds  faster, 
Fig.  35,  in  younger  embryos,  and  that 
in  very  young  embryos  the  daily  in- 
crease is  simply  enormous.  For,  as  I 
have  demonstrated  on  a  previous  occa- 
sion, it  may  reach  in  very  young  em- 
bryos the  value  of  at  least  1000  per 
cent.  Professor  Donaldson38  of  the 
Wistar  Institute  has  already  published 
more  exact  data  as  to  the  weight  of 
embryos  of  the  white  rat.  He  has 
collected  further  data,  and  we  may 
expect  from  him  a  detailed  memoir  on 
embryonic  growth.  He  has  completely 
confirmed  my  result  that  there  occurs 
an  enormous  decrease  in  the  rate  of 
growth  during  embryonic  life.  These 
investigations  lead  us  to  the  conclusion 
that  the  diminution  in  the  rate  of 
growth  occurs  chiefly  during  the  first 
developmental  periods,  and  that  the 

diminution  after  birth  is  very  gradual.  Hence  if  we 
seek  for  the  cause  of  this  diminution,  the  facts  indi- 
cate that  we  should  investigate  the  conditions  during 
embryonic  life  because  this  is  the  period  of  loss  We 


500% 


400% 


300°/6 


200% 


100% 


01    23^56789  10 
FIG.  35. — Curve  of  the 
monthly  increase  in  weight 
of  the  human  embryo. 


72  THE   EVOLUTION    QF_PEATH 

may  therefore  expect  that  the  changes  which  cause  the 
diminution  wll  be  more  noticeable  in  embryos  than  in  older 
animals. 

I  have  not  succeeded  in  determining  with  absolute  cer- 
tainty the  cause  of  the  inhibition  of  growth.  We  find, 
however,  a  close  correlation  between  the  alterations  which 
occur  in  the  cells  of  the  embryo  and  the  inhibition,  which 
renders  it  probable  that  the  alterations  of  the  cells  are  at 
least  one  essential  cause  of  the  diminution  of  the  growth. 
The  alterations  which  here  come  into  play  are  those  of  differ- 
entiation, and  in  fact  differentiation  proceeds  in  young 
embryos  with  extraordinary  rapidity  and  in  older  embryos 
more  slowly.  At  the  time  of  tiirth  the  differentiation  is  for 
the  most  part  far  advanced,  and  thereafter  continues  extraor- 
dinarily slowly.  Up  to  the  present  at  least  it  has  been  im- 
possible to  express  our  observations  of  the  rapidity  of  differ- 
entiation in  statistical  form  because  we  do  not  yet  know  how 
to  measure  differentiation  quantitatively.  We  can  merely 
estimate  the  degree  of  differentiation.  In  spite  of  the 
incomplete  reliability  of  this  method,  I  believe  that  the  es- 
timate which  has  been  made  answers  to  the  truth.  That  a 
causal  relation  exists  between  the  diminution  of  differentia- 
tion and  the  rate  of  growth  is  confirmed  by  the  fact  that 
direct  observation  teaches  us  that  undifferentiated  cells 
may  divide  rapidly  and  that  differentiated  cells  divide  more 
slowly,  and  finally  that  the  most  completely  differentiated 
cells  do  not  divide  at  all.  The  indicated  considerations  have 
led  me  to  the  conclusion  that  differentiation  is  to  be  con- 
sidered the  essential  cause  of  senescence. 

I  have  already  asked  you  to  give  heed  to  the  fact  that 
differentiation  occurs  principally  as  a  transformation  of  proto- 
plasm. At  the  same  time  we  learn  that  in  order  to  render  the 


THE   EVOLUTION    OF   DEATH  73 

differentiation  possible  the  protoplasm  must  grow  in  order 
to  furnish  the  basis  for  the  differentiation.  Hence  I  should 
/like  to  give  the  above  conclusion  the  following  form: 
Senescence  is  caused  by  the  increase  and  differentiation  of  pro- 
toplasm. 

The  correctness  of  this  conclusion  is  strengthened  by  the 
fact  that  we  find  the  opposite  relations  in  young  cells  which 
have  characteristically  a  nucleus  with  little  undifferentiated 
protoplasm.  During  the  development  of  the  ovum  there 
arise  at  first  relatively  large  cells  which  develop  further,  and 
through  numerous  generations  became  steadily  smaller. 
Since  the  ovum  usually  contains  a  nutritive  yolk,  the  cells  grow 
by  assimilating  the  yolk.  The  brilliant  investigations  of 
Conklin32  have  shown  that  during  the  segmentation  of  the 
ovum  not  only  is  the  total  amount  of  nuclear  substance  in- 
creased, but  also  the  total  amount  of  protoplasm  in  the  strict 
sense.  It  comes  about,  however,  that  the  increase  of  the 
nucleus  is  relatively  greater  than  the  increase  of  protoplasm. 
Conklin  determined  in  Crepidula  that  in  the  two-celled  stage 
the  nuclei  form  only  0.0117  of  the  total  volume  of  the  ovum, 
but  in  the  twenty-four-celled  stage  they  form  0.0255  of  the 
volume.  Soon  there  follows  a  stage  with  really  young  cells,  as 
I  have  above  defined  them .  We  distinguish  two  chief  periods 
of  development.  The  first  is  much  the  shorter  and  is  char- 
acterized by  the  preponderating  increase  of  the  nuclei.  The 
second  is  much  longer  and  is  marked  by  the  growth  and  dif- 
ferentiation of  the  protoplasm.  The  first  is  the  period  of 
rejuvenation,  the  second  the  period  of  senescence  or  growing 
old. 

A  remark  must  be  here  intercalated.  The  rate  of  growth 
and  of  the  division  of  the  cells  does  not  depend  solely  upon  the 
organization  of  the  cells  itself  for  the  time  being.  The  degree 


74  THE   EVOLUTION   OF   DEATH 

of  potential  capacity  to  grow  and  to  divide  is  presumably 
fixed  by  the  organization  of  each  cell,  but  there  occur  in  the 
body  inhibiting  influences,  perhaps  also  exciting.  Thus  it 
may  happen  that  a  cell  potentially  capable  of  division  cannot 
divide,  or  that  a  cell  which  has  long  remained  inactive  may 
be  excited  to  division  by  special  newly  arisen  influences.  The 
phenomena  are  by  no  means  simple. 

The  theory  of  senescence  which  I  have  expounded  to  you 
was  proposed,  as  you  have  heard,  by  myself.  All  achieve- 
ments of  science  originate  in  this  way.  They  are  at  first 
purely  personal.  Afterward  when  they  have  been  tested  they 
acquire  general  validity.  And  so  with  regard  to  my  theory, 
until  the  discussion  is  concluded  we  must  wait  in  order  to 
decide  whether  this  theory  or  some  other  which  may  be 
brought  forward  is  to  be  finally  adopted. 

Some  of  the  theories  of  senescence  we  may  now  discuss 
briefly.  That  of  Conklin  has  been  previously  mentioned.  I 
have  already  indicated  to  you  the  reasons  which  lead  me  to 
designate  these  theories  as  insufficient.  There  are  besides  a 
number  of  theories  which  have  been  conceived  from  a  purely 
medical  point  of  view,  and  which  are  little  adapted  to  satisfy 
a  biologist.  First  of  all  must  be  named  the  theory  of  Mets- 
chnikoff,  of  which  probably  all  cultivated  men  have  heard. 
The  Russian  investigator,  who  has  been  working  for  many 
years  in  the  Pasteur  Institute  in  Paris,  published  in  the  year 
1903  a  peculiar  book  with  the  title,  "La  nature  de  Fhomme." 
With  the  views  of  life  presented  therein,  we  have  at  present 
nothing  to  do.  We  restrict  ourselves  to  the  discussion  of  the 
theory  of  disharmonies  presented  in  this  book.  According  to 
Metschnikoff,  a  disharmony  arises  whenever  the  structure 
of  an  organ  is  incompletely  adapted  to  the  needs  of  the  body. 
The  disharmonies  he  mentioned  do  not  seem  to  me  very 


THE   EVOLUTION    OF   DEATH  75 

important,  for  they  refer  for  the  most  part  to  structures  whose 
physiological  significance  we  do  not  know.  It  is  venturing 
much  to  conclude  from  our  ignorance  that  a  disharmony 
exists.  To  one  physiological  disharmony,  which  he  be- 
lieves he  has  discovered,  our  author  attributes  the  very 
greatest  importance.  He  is  of  the  opinion  that  our  large 
intestine  is  too  large,  and  that  there  occur  in  it  fermentations 
which  produce  toxic  substances  which  then  act  to  poison  the 
body.  He  believes  further  that  these  unfavorable  conditions 
become  very  serious  in  man  with  increasing  age,  and  he 
attributes  especially  to  them  the  difficulties  of  the  very  old. 
In  order  to  avoid  these  weaknesses  he  recommends  a  treatment 
which,  according  to  him,  is  adapted  to  the  suppression  of  the 
fermentations  in  the  large  intestine.  The  treatment  is 
simple,  for  it  consists  in  drinking  sour  milk.  According  to  his 
theory  the  germs  pass  with  the  milk  into  the  intestine,  where 
they  inhibit  the  toxic  fermentations.  It  has  become  in  the 
highest  degree  improbable  that  the  fermentations  in  the 
large  intestine  have  the  significance  ascribed  to  them  by 
Metschnikoff,  but  even  if  he  is  right  his  discovery  brings  no 
explanation  of  senility,  as  indeed  senescence  is  a  very  wide- 
spread phenomenon  and  occurs  also  in  animals  and  plants 
which  have  no  large  intestine. 

With  how  little  seriousness  Metschnikoff  has  fomulated 
his  theory  will  be  clear  to  anyone  who  reads  an  article  by 
the  American  physiologist,  C.  A.  Herter.34  Herter,  whose 
early  death  means  a  heavy  loss  for  science,  showed  that  we 
have  as  yet  no  proof  that  sour  milk  has  any  influence  whatever 
on  the  bacterial  flora  of  the  large  intestine,  and  also  no  proof 
that  such  an  influence  would  be  rather  beneficial  than  injurious 
to  man.  The  problem  of  intestinal  fermentations  is  ex- 
ceedingly complicated. 


76  THE    EVOLUTION    OF   DEATH 

A  similar  criticism  may  be  directed  against  the  current 
medical  theory  of  growing  old  which  seeks  to  explain  the 
observed  weaknesses  and  difficulties  of  old  men  by  the 
condition  of  their  blood-vessels,  especially  of  their  arteries. 
Thus  Osier  has  said  a  man  is  as  old  as  his  arteries.  This  view 
rests  upon  clinical  experiments,  for  in  fact  the  disturbances 
in  the  case  of  senile  weakness,  which  are  occasioned  by  the 
altered  structure  of  the  walls  of  the  vessels,  are  especially 
noticeable  and  yield  valuable  symptoms  for  the  diagnostician. 
We  have,  however,  to  do  with  the  consequences,  not  with  the 
causes,  of  senility. 

Professor  Mlihlmann  has  also  written  repeatedly  concerning 
extreme  old  age  and  his  memoirs  contain  many  interesting 
and  valuable  statements.  He  offers  us  also  an  explanation 
of  senility.  The  latest  memoir  of  Miihlmann35  of  which  I 
know,  and  which  must  be  here  considered,  appeared  in  the 
year  1910.  In  it  he  discusses  my  theory.  The  present 
opportunity  does  not  appear  to  me  suited  to  discuss  Miihl- 
mann's  critic  fully  and  to  answer  it.  Permit  me  to  direct 
your  attention  to  it,  because  quiet  discussion  leads  to  the 
settlement  of  scientific  problems.  I  venture  to  add  that 
I  am  still  convinced  that  my  view  can  be  successfully  defended 
against  Miihlmann's  attack.  Miihlmann  writes,  strictly 
speaking,  from  the  medical  point  of  view,  or  in  other  words 
from  an  anthropomorphic  point  of  view.  He  is  concerned 
with  rendering  the  phenomena  in  man  more  comprehensible 
without  having  regard  to  the  corresponding  phenomena  as 
they  occur  in  living  organisms  in  general.  Investigations 
which  are  conducted  by  such  thoughts  as  we  know  from 
experience  lead  to  valuable  results.  They  can,  however, 
only  exceptionally  bring  forth  results  which  are  com- 
pletely satisfying  to  biologists.  Miihlmann  attributes 


THE   EVOLUTION    OF   DEATH  77 

I 

special  importance  and  meaning  to  the  outer  surfaces  of  the 
body,  and  to  the  consequences  involved  in  the  greater  or  less 
remoteness  of  the  single  parts  of  the  body  from  the  outer 
surfaces.  It  is  very  possible  that  these  results  have  signifi- 
cance for  the  physiological  activities  of  the  body,  and  it  is 
not  improbable  that  with  the  increasing  age  the  proportion  of 
the  outer  surfaces  to  the  rest  of  the  body  becomes  unfavor- 
able. This  interpretation  with  other  related  suppositions 
is  presented  by  Miihlmann.  He  believes  further  that  the 
mentioned  results  act  to  the  disadvantage  of  the  central 
nervous  system  by  which  the  gradual  destruction  of  this 
system  is  caused,  a  destruction  which  progresses  until  it 
brings  about  natural  death.  Miihlmann's  demonstration  is 
not  convincing  to  me,  but  even  if  we  should  grant  that  he  is 
right,  and  accept  his  conclusion  that  natural  death  in  man  is 
directly  caused  by  degenerative  alterations  of  the  nerve  cells, 
we  should  still  not  have  won  a  general  biological  theory  of 
death.  As  we  have  already  heard,  the  death  of  cells  plays  a 
great  role  during  development  as  well  as  in  the  adult.  Any 
theory  of  death  must  reckon  with  these  facts  and  cannot  be 
sufficiently  valid  if  it  does  not  explain  both  the  natural  death 
of  the  whole  body  and  also  the  natural  death  of  the  cells 
which  are  continually  dying  off.  It  is  a  merit  of  the  theory  of 
cytomorphosis  that  it  maintains  its 'value  as  an  explanation 
of  all  forms  of  death. 

We  owe  to  Alexander  Gotte36  another  theory  which  I 
wish  to  mention  briefly.  According  to  this  theory,  natural 
death  is  closely  connected  with  the  phenomena  of  sexual 
reproduction,  for  it  assumes  that  the  maternal  organism  is 
exhausted  by  the  effort  of  reproduction,  which  thus  causes  the 
appearance  of  old  age.  We  must  pay  attention  to  the  fact 
that  it  was  not  until  after  the  appearance  of  Gotte's  article 


7  8  THE   EVOLUTION   OF   DEATH 

*  ,. 

in  the  year  1883  that  we  have  become  acquainted  with  the 
history  of  the  germ  cells.  Since  these  cells,  properly  speaking, 
develop  independently  of  the  somatic  cells,  it  becomes  very 
doubtful  whether  they  can  exert  any  such  influence  on  the 
body  as  Gotte's  theory  requires.  Moreover,  the  fact  that  a 
man  may  live  long  in  health  after  the  reproductive  capacity 
.is  lost  speaks  against  the  theory.  The  theory  of  Hansemann37 
may  be  considered  to  a  certain  extent  as  a  modification  of 
Gotte's.  Hansemann  seeks  the  immediate  cause  of  physio- 
logical death  in  the  atrophy  of  the  germ  plasm,  but,  as  we 
know,  senescence  is  not  a  phenomenon  which  begins  at  the 
end  of  life,  but  a  continuous  one  which  proceeds  in  young 
individuals  also.  It  is  therefore  clear  that  we  cannot  explain 
becoming  old  by  an  event  which  does  not  occur  until  the 
individual  is  already  old. 

The  various  hypotheses  which  we  have  just  discussed  have 
this  in  common,  that  they  seek  to  explain  only  the  death  of  the 
whole  body,  and  do  not  investigate  the  question  of  death  as  a 
phenomenon  of  cell  life.  The  theory  of  cytomorphosis  differs 
from  the  mentioned  theory  precisely  therein  that  it  regards 
death  as  a  phenomenon  which  occurs  in  single  cells.  It  is,  if 
I  am  right,  the  only  theory  which  we  possess  up  to  the  present 
time  which  answers  to  the  demands  of  biology. 

As  to  the  development  of  death  we  know  little  as  yet. 
Naturalists  assume  that  unicellular  organisms  were  developed 
in  the  world  earlier  than  the  multicellular,  or  in  other  words, 
that  they  are  more  primitive  and  older.  We  must  therefore 
assert  that  the  first  living  cells  were  potentially  immortal,  as  is 
at  present  the  case  for  their  existing  representatives.  From 
this  it  follows  that  natural  death  appeared  later.  It  seems  to 
me  probable  that  death  as  we  now  know  it  in  the  human  race 
was  evolved  gradually.  In  sponges  and  ccelenterates  we  find 


THE   EVOLUTION    OF   DEATH  79 

no  individualities  as  in  the  higher  animals.  A  part  of  a 
sponge  or  of  a  coral  may  die  and  the  other  part  continue  living, 
because  the  correlation  of  the  parts  has  not  advanced  so  far, 
but  in  these  animals  preservation  of  the  whole  is  independent 
of  the  preservation  of  the  correlation.  In  the  higher  animals 
the  correlation  is  much  more  intimate,  and  therefore  individ- 
uality more  marked,  until  we  reach  an  animal  whose  parts 
work  together  and  must  reach  definite  proportions  in  order 
that  the  working  together  may  be  properly  carried  out.  An 
organism  which  has  attained  higher  development  in  this  way 
cannot  continue  its  life  if  an  essential  part  or  an  essential 
organ  becomes  incapable  of  functioning.  We  know  that  the 
single  organs  must  have  their  specific  differentiation,  and  we 
know  further  that  these  differentiations  in  the  majority  of 
cases  increase  with  age,  and  that  it  may  go  so  far  that  the  cells 
of  a  special  organ  cannot  function  any  longer.  Now  if  an 
organ  which  is  essential  for  the  maintenance  of  the  whole 
body  gives  out,  the  entire  animal  must  die.  It  is  a  priori 
improbable  that  in  all  cases  natural  death  is  a  consequence  of 
the  alterations  of  the  same  organ.  Thus  we  know  that  in 
certain  insects  and  worms  death  occurs  almost  suddenly  after 
the  discharge  of  the  sexual  products,  yet  their  nervous  system 
may  be  intact.  We  may  admit  that  physiological  death  in 
man  is  caused  by  the  breakdown  of  the  nervous  system,  and 
yet  the  practicing  physician  sticks  to  his  opinion  that  death 
in  extreme  old  age  occurs  more  frequently  through  failure  of 
the  blood  vessels.  We  must  heed  the  fact  that  even  in  the 
highest  animals,  just  as  in  sponges  and  coelenterates,  parts  of 
the  body  may  break  down  without  causing  physiological 
death.  Permit  me  again  to  direct  your  attention  to  the  fact 
that  in  man  not  merely  single  cells  but  even  entire  organs  may 
die  off.  In  its  essence  the  phenomenon  in  these  cases  is  the 


8o  THE    EVOLUTION    OF   DEATH 

same  as  that  which  we  meet  on  a  larger  scale  in  the  ccelen- 
terates. 

Has  death  a  purpose?  Weissmann  has  expressed  the 
interesting  thought  that  death  is  advantageous  to  organisms. 
If  an  organism  lived  forever  it  would  become,  through  acci- 
dents, more  and  more  injured.  By  death  this  is  avoided,  and 
at  the  same  time  by  continuous  reproduction  the  creation  of 
new  healthy  individuals  is  provided  for.  I  am,  however,  not 
inclined  to  regard  death  in  itself  as  advantageous,  but  rather 
as  a  consequence  of  differentiation.  The  higher  plants  and 
animals  have  arisen  through  differentiation — to  it  we  are 
indebted  for  our  organization  which  makes  us  men;  to  it  we 
owe  the  possibility  of  knowing  our  earth,  its  inhabitants,  and 
ourselves;  to  it  we  owe  all  advantages  of  our  existence;  to  it 
we  owe  the  possibility  of  carrying  on  our  physiological  work 
much  better  than  the  lower  organisms;  to  it  we  owe  the  possi- 
bility of  those  human  relations  which  are  the  most  precious  of 
our  experiences.  These  advantages  and  many  others  do  we 
owe  to  differentiation,  the  price  of  which  is  death.  The  price 
is  not  too  high.  None  of  us  would  like  to  return  to  the  condi- 
tion of  a  lower  organism  which  might  be  capable  of  continuing 
its  species,  and  which  had  to  suffer  death  only  through  acci- 
dent. We  pay  the  price  willingly.  Natural  death  comes,  as 
we  now  know,  when  an  essential  part  of  the  body  yields.  It 
may  be  the  brain;  it  may  be  the  heart;  it  may  be  another 
organ,  in  which  the  cytomorphosis  goes  so  far  that  the  organ 
can  no  longer  perform  the  work  assigned  to  it,  and  when  it 
fails  it  brings  the  whole  to  rest.  Thus  the  conception  of 
death  shapes  itself  in  our  minds.  The  mystery  remains.  The 
biologist  knows  the  essence  of  death  no  better  than  the  essence 
of  life.  We  say  of  certain  bodies  that  they  live,  of  others 
that  they  are  dead.  Science  at  present  is  incapable  of  telling 


THE    EVOLUTION    OF   DEATH  8 1 

us  what  the  difference  between  these  two  conditions  is,  but 
we  are  learning  every  year  more  about  life  and  more  about 
death,  and  we  hope  that  with  coming  years  our  biological 
science  will  so  grow  that  she  will  make  both  life  and  death 
comprehensible. 


V. 
THE  DETERMINATION  OF  SEX. 

Your  Excellency! 

There  is  probably  no  phenomenon  which  has  always 
seemed  to  mankind  at  once  so  interesting  and  so  mysterious 
as  sex.  A  history  of  the  opinions,  speculations,  and  customs 
which  have  arisen  in  the  course  of  time  in  connection  with  the 
question  of  sex  would  be  instructive.  The  progress  of  science 
has  recently  made  us  acquainted  with  the  material  basis  of  the 
phenomenon.  The  most  important  notion  we  have  acquired 
is  that  of  the  difference  between  sex  and  sexuality.  We 
derive  our  notion  of  sex  from  our  repeated  experiences  in 
connection  with  man  and  with  domestic  animals.  We  know 
from  our  daily  life  that  male  individuals  possess  many  pecul- 
iarities which  the  females  do  not  have,  and  vice  versa.  By  the 
application  of  the  microscope  we  have  discovered  sexuality 
proper,  which  is  not  characteristic  for  the  male  or  female 
body,  but  is  peculiar  exclusively  of  the  sexual  products.  An 
animal  or  plant  is  a  male  or  female  according  as  the  individual 
in  question  produces  ova  or  spermatozoa  (pollen  grains). 
We  note  often  that  secondary  peculiarities  have  been  devel- 
oped in  connection  with  this  fundamental  difference.  The 
secondary  peculiarities  are  pronounced  in  man  and  the  higher 
animals.  One  of  the  most  interesting  books  which  we  owe  to 
Darwin  deals  brilliantly  with  the  problem  of  the  origin  of  the 
so-called  secondary  sexual  characteristics.  They  are  really 
secondary  and  without  doubt  a  consequence  of  the  sexual 

82 


THE   DETERMINATION    OF    SEX  83 

difference,  the  essence  of  which  consists  in  the  production  of 
eggs  or  spermatozoa. 

By  no  means  seldom  do  we  find  animals  or  plants  which 
are  hermaphroditic  organisms  and  produce  both  sexual 
elements.  Biologists  very  commonly  hold  the  opinion  that 
hermaphroditism  represents  the  primitive  relation.  Analysis 
of  the  relations,  however,  seems  to  me  not  to  lead  to  this 
conclusion,  and  I  propounded  in  1892  the  hypothesis39  that 
originally  every  animal  individual  is  sexually  indifferent. 
Expressed  in  this  form  the  hypothesis  is  not  exact.  It  may 
be  more  correctly  expressed  thus:  This  sexually  indifferent 
condition  is  primitive.  We  learned  in  the  third  lecture  the 
history  of  the  sexual  cells.  These  cells,  however,  are  not  sex- 
ual elements,  but  every  one  of  them  must  pass  through  a 
very  complicated  and  remarkable  transformation  in  order  to 
become  a  sexual  element.  This  fact  in  my  opinion  renders  it 
certain  that  the  primitive  condition  was  an  indifferent  one. 
After  it  ensue  the  alterations  which  transform  a  sexless  into 
a  sexual  individual. 

When  a  cell  divides  the  nucleus  usually  passes  through  a 
so-called  mitotic  change  which  leads  to  the  division  of  the  nu- 
cleus. During  this  change  chromosomes  appear.  Each  chro- 
mosome is  a  separate  granule  which  is  formed  by  the  concen- 
tration of  a  small  part  of  the  nucleus,  Fig.  n.  After  the  divi- 
sion is  completed  the  chromosomes  become  indistinct  and  are 
at  the  same  time  utilized  for  the  restoration  of  the  normal 
structure  of  the  resting  nucleus.  Hence  the  chromosomes  are 
visible  only  during  the  process  of  division.  It  has  been  ascer- 
tained that  the  number  of  chromosomes  in  each  species  is  con- 
stant,* although  in  different  species  their  number  may  vary 

*  This  statement  is  not  exact,  for  in  certain  cases,  ascaris,  etc.,  the  number 
of  chromosomes  varies  with  the  period  of  life,  and  it  is  probable  that  in  somatic  cells 


84  THE   DETERMINATION    OF    SEX 


between  wide  limits.  We  have  also  discovered  that  the  num- 
ber of  chromosomes  in  the  sexual  elements  in  every  species 
which  has  been  adequately  investigated  is  about  half  the  num- 
ber of  chromosomes  occurring  in  the  somatic  cells.  When 
sexual  products  arise  from  the  sexual  cells,  each  cell  divides 
twice  in  rapid  sequence,  so  that  four  sexual  elements  arise. 
When  male  elements  arise  all  four  cells  normally  develop. 
An  interesting  and  instructive  exception  will  be  considered 
presently.  In  the  case  of  four  female  elements,  on  the  con- 
trary, only  one  cell  enlarges  and  becomes  an  ovum.  The 
three  other  cells,  which  have  long  been  known  by  the  name  of 
polar  globules,  break  down.  If  we  count  the  chromosomes 
which  appear  during  this  double  division,  we  find  in  typical 
cases  that  their  number  is  reduced  one  half,  so  that  at  the 
close  of  the  process  we  have  cells,  the  so-called  sexual  elements, 
which  contain  only  half  as  many  chromosomes  as  the  cells 
of  the  body,  and  the  original  sex  cells.  More  careful  in- 
vestigations have  taught  us  further  that  the  reduction  in 
the  number  of  chromosomes  is  not  always  exactly  to  one- 
half.  We  find  in  certain  cases  one  or  several  extra  chromo- 
somes. The  origin  and  significance  of  these  extra,  or  ac- 
cessory, chromosomes  has  been  studied  especially  in  America. 
American  investigations  have  yielded  the  very  important 
result  that  the  accessory  chromosomes  stand  in  immediate 
relation  to  the  determination  of  sex.  To  collect  the  facts 
has  cost  many  years  of  difficult  labor.  These  facts  have 
made  it  clear  that  in  all  higher  plants  and  animals  we 
encounter  two  fundamentally  different  species  of  cells;  first, 
ordinary  cells  with  the  full  number  of  chromosomes;  second, 
special  cells  which  we  know  as  sexual  elements,  or  sexual 

the  number  of  chromosomes  is  subject  to  minor  variations.  Compare  H.  L.  Wieman's 
article  in  the  number  for  May,  1913,  of  the  American  Journal  of  Anatomy. 


THE   DETERMINATION    OF    SEX  85 

products,  which  are  characterized  by  the  reduced  number  of 
chromosomes.  We  are  now  in  a  position  to  distinguish  sexual 
elements  and  body  cells  by  a  visible  microscopic  character- 
istic, and  hence  to  define  the  two  fundamental,  forms  of  cells. 
A  cell  is  only,  then,  a  sexual  element  when  it  has  the  reduced 
number  of  chromosomes.  The  sexual  cells  have  sexuality. 
The  body  in  which  the  sexual  elements  are  brought  to  develop- 
ment may  have  sex.  The  basis  of  all  clear  thinking  in 
regard  to  the  questions  of  sex  is  the  difference  between  sex  and 
sexuality. 

How  is  sex  determined?  As  yet  we  cannot  explain  the 
relations  in  hermaphrodites  at  all.  We  know  only  that  they 
have  indifferent  sexual  cells,  out  of  which  may  be  formed  male 
and  female  elements  either  at  one  time,  or  from  time  to  time,  or 
at  different  periods  of  life.  We  assume  that  the  occurrences 
are  regulated  by  internal  conditions  of  the  hermaphroditic 
organism.  We  have  also  discovered  that  external  conditions 
may  under  certain  conditions  influence  the  sexual  develop- 
ment of  hermaphrodites,  thus,  for  example,  in  melons,  which 
normally  produce  male  and  female  flowers  on  the  same  plant, 
under  the  influence  of  higher  temperature  only  male  flowers 
develop,  and  under  the  influence  of  shade  only  female.  How 
these  results  come  about  is  completely  unknown. 

The  investigation  of  forms  of  separated  sex  has  proved 
more  valuable.  Investigators  have  long  endeavored  to  dis- 
cover influences  which  might  determine  the  sex  of  an  ovum 
during  its  development.  For  some  time  it  was  hoped  to  learn 
something  from  the  investigation  of  the  proportion  of  the 
sexes  in  various  species.  The  sexual  relation  is  usually  cal- 
culated by  setting  the  number  of  females  as  =  100,  and  then 
expressing  the  number  of  males  in  percentage  of  the  number 
of  females.  These  investigations  have  as  yet  yielded  no 


86  THE   DETERMINATION    OF    SEX 

important  generalizations.     How  great  the  variations  are  is 
shown  by  the  following  table: 

PER  CENT.  OF  MALES. 

Loligo 16.6       Man 106.9(105.3?) 

Octopus 33-3       Domestic  dog 138.0 

Horse 98.3       Cottus 188.0 

Songbirds 100.0      Lophius 385.0 

Herring 101.0      Latrodectus 819.0 

Cat 105.0 

There  are  two  series  of  cases  known  in  which  the  sex 
is  determined  in  advance.  The  first  series  comprises  several 
species  of  animals  of  various  classes  which  produce  two  sorts 
of  eggs,  differing  in  size.  Such  eggs  occur  for  example  in 
the  worm  Dinophilus,  in  many  rotifers,  as,  for  instance, 
Hydatina,  in  daphnids,  in  Phylloxera,  and  other  forms.  The 
large  eggs  produce  only  females,  the  smaller  only  males.40 
Oskar  Schultze  was  induced  by  these  facts  to  maintain  that 
sex  is  determined  in  the  ovum.  More  recent  discoveries  have 
rendered  Schultze's  theory  superfluous. 

The  second  series  of  cases  is  afforded  by  the  eggs  especially 
of  various  insects  which  may  be  developed  parthogenetically, 
as  occurs,  for  example,  in  Phylloxera.  The  fertilized  ova 
produce  females  only,  the  unfertilized  on  the  contrary, 
according  to  conditions,  either  males  or  females.  For  a  long 
time  it  was  hoped,  though  in  vain,  to  secure  the  explanation  of 
the  determination  of  sex  by  the  exact  study  of  such  ova. 

Naturalists  have  long  directed  their  efforts  toward  dis- 
covering external  conditions,  the  action  of  which  determines 
sex.  It  appears  now  to  be  established  that  under  certain 
conditions  the  proportions  of  the  sexes  may  be  altered  by  ex- 
ternal conditions.  The  experiments  of  Richard  Hertwig, 
which  he  published  in  1907,  excited  great  interest.  They  have 
been  extended  by  his  pupil,  Kuschkakewitz.41  Hertwig 


THE   DETERMINATION   OF    SEX  87 

demonstrated  that  delayed  fertilization  of  frogs'  eggs  produces 
an  excess  of  males.  Unfortunately  it  is  not  clear  how  this 
result  is  brought  about.  An  American  lady,  Miss  King,  has 
made  extensive  investigations 42  upon  the  influence  of  external 
conditions  on  the  determination  of  sex  in  toads'  eggs.  Nutri- 
tion and  temperature  are  apparently  without  effect,  but  if  the 
eggs  lose  water  then  more  females  develop.  Even  if  we  should 
pass  in  review  the  entire  literature  upon  the  determination  of 
sex  through  external  conditions  we  should  not  get  much 
further  than  we  could  from  the  examples  I  have  presented  to 
you.  We  are  safe  in  saying  that  external  conditions  are  prob- 
ably not  of  great  importance,  and  at  the  most  are  merely  fav- 
orable or  unfavorable  for  the  development  of  one  sex  or  the 
other.  The  essential  conditions  must  be  sought  in  the  cells 
themselves,  and  this  view  has  had  brilliant  confirmation 
through  recent  researches. 

It  is  very  pleasant  for  me  as  exchange  professor  to  have 
the  privilege  of  reporting  a  series  of  American  investiga- 
tions which  are  of  the  highest  value  because  they  have  pro- 
cured for  us  entirely  new  views  of  the  determination  of  sex. 
Only  recently  have  similar  investigations  been  entered  upon 
in  Europe.  The  new  doctrine  arose  from  the  observation  of 
the  developmental  processes  which  lead  to  the  formation  of 
the  male  elements  in  certain  insects.  The  founder  of  the  doc- 
trine is  Professor  C.  E.  McClung,43  who,  after  serving  many 
years  at  the  University  of  Kansas,  became  last  autumn 
Professor  of  Zoology  at  the  University  of  Pennsylvania  in 
Philadelphia.  His  first  memoir  upon  the  spermatogenesis  of 
insects  appeared  in  the  year  1900,  and  contains  the  results  of 
his  investigations  on  the  process  in  the  Acrididse.  McClung's 
most  important  discovery  was  that  one  chromosome  during 
the  evolution  of  the  sexual  elements  behaves  quite  differently 


88  THE   DETERMINATION    OF    SEX 

from  the  rest.  It  appears  when  a  sexual  cell  begins  its  trans- 
formation. At  this  time  the  chromosomes  arise  in  the  reduced 
number  and  it  is  easy  then  to  distinguish  the  one  chromosome 
which  McClung  has  named  the  accessory.  When  the  sexual 
cell  has  formed  the  reduced  number  of  chromosomes  it  is  called 
a  spermatocyte.  The  spermatocyte  divides,  and  at  the  same 
time  all  the  chromosomes,  including  the  accessory,  also  divide. 
The  two  daughter  cells  quickly  divide  again  and  so  also  do 
the  ordinary  chromosomes,  but  this  time  the  accessory  chromo- 
some does  not  divide,  but  passes  undivided  into  one  of  the  daughter 
cells  of  the  second  generation.  In  this  way  four  cells  arise  as 
always  in  spermatogenesis,  and  of  these  four  cells  two  have 
each  an  accessory  chromosome  and  two  have  none  such.  The 
four  cells  pass  through  further  changes  in  order  to  become 
mature  spermatozoa.  Thus  it  comes  about  that  we  have  in 
these  insects  two  kinds  of  spermatozoa,  for  half  of  them  con- 
tain a  piece  of  the  accessory  chromosome  and  the  other  half 
do  not.  From  these  facts  McClung  drew  the  conclusion  that 
the  two  kinds  of  spermatozoa  determine  the  sex,  and  since  he 
found  the  accessory  chromosomes  in  the  cells  of  the  male  body, 
he  further  supposed  that  the  accessory  chromosomes  have  to 
do  with  the  creation  of  the  male  sex.  The  observations  of 
the  Kansas  zoologists  have  been  repeatedly  confirmed  by 
other  Americans.  They  are  so  easily  made  and  are  so  signifi- 
cant that  we  have  demanded  for  several  years  past  that  our 
medical  students  at  Harvard  should  study  the  spermatogenesis 
of  grasshoppers.  That  the  accessory  chromosome  stands  in 
immediate  relation  to  the  production  of  sex  must  be  considered 
as  established,  but  I  must  immediately  call  your  attention  to 
the  fact  that  McClung's  theory  acquired  an  essential  further 
development  through  E.  B.  Wilson,44  who,  in  the  investigation 
of  the  relations  of  chromosomes  in  female  insects,  was  able 


THE   DETERMINATION    OF    SEX  89 

to  demonstrate  that  the  accessory  chromosome  does  not 
determine  the  formation  of  males  but  of  females.  The  ac- 
cessory chromosome  was  first  seen  by  a  German,  Henking, 
and  was  afterward  studied  by  the  American,  Montgomery. 
McClung  was  the  first  to  recognize  its  true  nature  and  import- 
ance, and  to  him  belongs  the  honor  of  having  first  brought  the 
investigation  of  the  determination  of  sex  upon  the  proper  road. 

The  formation  of  the  sexual  elements  is  full  of  meaning 
and  interest,  but  it  cannot  be  made  clear  by  words  alone. 
On  account  of  the  importance  of  the  phenomenon  I  wish  now 
to  show  you  certain  pictures  which  are  suited  to  clarify  your 
impressions. 

The  sexual  cells,  like  all  cells,  are  little  adapted  in  their 
natural  state  to  microscopic  observation.  Special  methods 
have  been  invented  to  overcome  this  difficulty.  In  most  cases 
thin  sections  are  made  of  the  organ  or  tissue  which  it  is  de- 
sired to  investigate.  The  sections  are  artificially  colored. 
We  should  have  been  able  to  learn  little  of  the  structure  of 
cells  without  this  method.  The  pictures  which  I  have  to 
present  to  you  have  been  made  from  artificially  colored  prepa- 
rations. The  chromosomes  which  we  wish  specially  to  ob- 
serve are  colored  almost  black,  while  most  of  the  rest  of  the 
cell  appears  gray.  Our  pictures  are  all,  except  Fig.  44,  draw- 
ings for  the  most  part  from  photographs.  In  the  drawings 
only  the  black  parts  have  been  put  in,  and  in  most  of  them 
only  the  chromosomes  are  represented.  When  a  sexual  cell 
begins  to  transform  itself  into  a  sexual  element  the  nucleus 
passes  through  a  series  of  changes  during  which  the  chromo- 
somes assume  wonderfully  irregular  forms,  which,  however, 
quickly  change  again.  Our  first  picture*  is  a  drawing  by  a 

*  The  picture  mentioned  was  projected  on  the  screen  for  the  lecture,  and  is  not 
reproduced  here.  The  conditions  are  similar  to  those  represented  in  Fig.  52. 


THE   DETERMINATION    OF    SEX 


student  of  the  sexual  cells  of  a  grasshopper  such  as  all  our 
students  are  given  opportunity  to  see.  In  every  nucleus  one 
finds  a  single  round,  dark  body,  the  ac- 
cessory chromosome.  The  remaining 
chromosomes  are  all  drawn  out  and  have 
irregular  outlines,  so  that  the  accessory 
chromosome  is  conspicuous. 

Our  next  pictures,  Figs.  36-40,  are 
taken  from  Anasa  tristis,  and  are  after 
drawings  by  Miss  Pinney.  Anasa  tristis 
is  a  species  of  Hemiptera  very  common 
with  us.  The  spermatogenesis  of  this 
insect  has  been  investigated  by  many 
Americans:  by  F.  C.  Paulmier  1899,  by  E. 
B.  Wilson  1905  and  1907,  by  Miss  Foote 
and  Miss  Strobell  1907,  by  Professor 
Lefevre  and  Miss  McGill  1908,  by  C.  V. 
Morril  1901,  and  by  Professor  McClung 
and  Miss  Pinney  1911.  Anasa  has  become, 
so  to  speak,  a  classic  animal.  As  the  statements  of  earlier  in- 
vestigators did  not  completely  agree,  Professor  McClung  and 
Miss  Pinney  made  a  careful  reinvestigation.  They  had  at 
their  disposal  in  part  the  material  used  by  their  predecessors. 


FIG.  36.  — A  n  a  s  a 
tristis.  A  section  of  a 
spermatogoneal  cyst. 
The  peculiar  arrange- 
ment of  the  spindle  is 
characteristic. 


FIG.  37. — Anasa  tristis.  Successive  stages  in  the  transformation  of  the  nucleus  of 
a  sexual  cell  (spermatogonium).  The  transformation  is  the  preparation  for  the 
development  of  the  sexual  element. — After  Edith  Pinney. 

Their  memoir  is  excellent,  and  I  present  a  selection  of  their 
pictures.     We  will  consider  first  the  commencement  of  the 


THE   DETERMINATION   OF    SEX  91 

transformation  of  the  sexual  cells.  Fig.  36  shows  a  group  of 
cells,  the  nuclei  of  which  have  assumed  the  spindle  form.  We 
see  clearly  the  fibers  of  the  spindle  and  the  chromatine  col- 
lected in  the  middle  of  each  spindle.  The  chromatine  con- 
sists of  chromosomes  which  lie  crowded  together.  The  re- 
maining pictures  which  we  have  to  consider  represent  merely 
the  nuclei.  Fig.  37  shows  the  successive  alterations  which  the 


FIG.  38. — Anasa  tristis.  Spermatocyte  nucleus  in  preparation  for  the  first 
division,  x,  the  accessory  chromosome;  p,  the  plasmasome,  a  transitory  structure 
which  does  not  belong  to  the  chromosomes,  but  soon  dissolves. 

nucleus  of  a  sexual  cell  passes  through  when  it  begins  to  trans- 
form itself  into  a  sexual  element.  Soon  an  accessory  chromo- 
some becomes  distinct,  especially  in  the  stages  shown  in 
Fig.  38,  during  which  the  chromosomes  become  again  dissolved 
except  the  accessory,  which  behaves  independently  and  main- 
tains its  integrity.  The  accessory  chromosome  has  no  ab- 
solute constant  form,  but  varies  greatly.  Many  of  these 
variations  have  been  pictured  by  Miss  Pinney.  Fig.  39 
leads  us  to  the  first  development  of  the  sexual  cell  (first 
spermatocyte).  We  recognize  easily  the  spindle  figure. 
Out  of  the  dissolving  skein  of  chromatine  complete  chromo- 
somes have  arisen.  The  accessory  chromosome  lies  always 
at  the  side  of  the  others.  All  the  chromosomes  divide,  and 
we  can  observe  readily  in  the  figures  how  the  two  groups  of 
chromosomes  diverge  and  move  toward  the  poles  of  the 
spindle.  In  each  group  there  is  one  chromosome  which  has 
been  formed  by  the  division  of  the  accessory.  The  four  draw- 
ings in  the  lower  part  of  Fig.  39  from  right  to  left  illustrate  the 


92 


THE    DETERMINATION    OF    SEX 


progressive  division  of  the  cell.  We  notice  that  in  each  of  the 
daughter  cells  there  is  an  accessory  element.  In  ordinary 
cell  division  the  chromosomes  form  in  the  daughter  cells  a  new 
nucleus  which  assumes  the  resting  form,  in  which  we  can  no 
longer  distinguish  the  single  chromosomes.  In  the  case  of  the 
developing  sexual  elements,  however,  no  resting  nucleus  is 
produced  because  the  cell  at  once  proceeds  to  a  second  division. 


FIG.  39. — Anasa  tristis.     Division  of  the  first  spermatocyte.     a,  b,  m,  ordinary 
chromosomes;  x,  accessory  chromosomes. 


Fig.  40  shows  us  the  successive  stages  of  the  second  division. 
During  it  all  the  chromosomes  divide  with  the  exception  of  the 
accessory,  which  does  not  divide  at  all,  but  migrates  into  one 
of  the  cells.  From  the  original  sexual  cell  there  have  now 
arisen  four  cells,  two  of  which  have  an  accessory  chromosome. 
The  four  cells  change  themselves  into  spermatozoa.  In  this 


THE   DETERMINATION    OF    SEX 


93 


31 


29 


FIG.  40.  —  Anasa  tristis.  Second  spermatocyte  division,  during  which  the  acces- 
sory chromosome  remains  undivided  and  partakes  itself  to  one  of  the  daughter  cells. 
x,  the  accessory  chromosome;  9,  two  groups  of  chromosomes;  19,  single  accessory 
chromosomes,  each  from  a  cell  in  the  stage  of  Nr.  18;  30,  three  daughter  nuclei  with 
the  accessory  chromosome;  31,  later  stages  of  the  same  (each  daughter  cell  forms  a 
spermatozoon).  —  After  Edith  Pinney. 


94 


THE   DETERMINATION    OF    SEX 


way  there  arise  two  kinds  of  spermatozoa.  When  an  egg  is 
fertilized  by  a  spermatozoon  that  contains  an  accessory  ele- 
ment, a  female  is  produced. 

Miss  Stevens46  has  published  a  series  of  papers  on  the  devel- 
opment of  the  sexual  elements.     Fig.  41  represents  the  alter- 


'- X 


FIG.  41. — Diabrotica.  a-d,  D.  vittata;  e-f,  D.  soror;  a,  dissolution  of  the  con- 
tracted chromosome  (first  stage  after  synizesis);  b-d,  transformation  of  the  nucleus 
of  the  first  spermatocyte;  x,  the  accessory  chromosome;  e-f,  division  of  the  nucleus 
of  the  first  spermatocyte. — After  N.  M.  Stevens. 

ations  as  found  by  her  in  a  beetle,  Diabrotica.  b,  c,  d  show 
the  accessory  chromosome  clearly,  e  and  /  show  us  the 
first  division.  Half  of  the  daughter  cells  of  the  first  division 
have  an  accessory  chromosome,  which,  however,  divides  at 
the  second  division.  The  process  differs  from  that  in  Anasa, 


THE   DETERMINATION   OF    SEX  95 

but  the  final  result  is  the  same,  for  there  are  formed  two  sexual 
elements  which  have  and  two  which  have  not  an  accessory 
chromosome.  Miss  Stevens  has  investigated  many  insects, 
as  also  has  E.  B.  Wilson.44  Both  have  made  similar  dis- 
coveries, and  they  have  been  able  to  demonstrate  that  the 
accessory  chromosome  is  not  always  single  but  may  appear 
in  certain  eggs  as  consisting  of  two,  three,  four,  or  even  five, 
parts.  They  have  also  observed  in  some  species  a  second 
accessory  chromosome,  which  they  have  designated  as  the 
Y-chromosome,  and  which  perhaps  also  plays  a  role  in  the 
determination  of  sex;-  but  it  must  not  be  confused  with  the 


FIG.  42 A.  FIG.  42B.  FIG.  43. 

FIG.  42. — Protenor  belfragei.  Chromosome  groups.  -4,  from  a  cell  of  a  female; 
B,  from  a  cell  of  a  male.  The  accessory  chromosomes  are-much  larger  than  the  ordi- 
nary ones. 

FIG.  43. — Protenor  belfragei.  Second  division  of  a  spermatocyte.  The  large 
accessory  chromosome  is  moving  undivided  toward  one  pole. 

true  accessory.  Professor  Wilson  has  had  the  kindness  to 
place  at  my  disposition  a  number  of  photographs*  of  his 
beautiful  preparations,  and  from  these  Figs.  42-51  have  been 
sketched.  In  Fig.  42  the  chromosomes  are  very  distinct.  In 
Fig.  42  A,  we  can  count  very  easily  twelve  ordinary  chromo- 
somes and  two  accessory.  Fig.  42  B  is  similar.  It  also  shows 
twelve  ordinary  chromosomes,  but  only  one  accessory.  The 

*  During  the  lecture  the  original  photographs  were  projected  by  the  lantern.  I 
use  this  opportunity  to  express  roy  very  sincere  thanks  to  Professor  Wilson,  both  for 
the  loan  of  the  photographs  and  for  his  generous  permission  to  make  drawings  from 
them. 


96  THE   DETERMINATION    OF    SEX 

first  of  the  two  pictures  is  from  the  cell  of  a  female,  the  second 
from  the  cell  of  a  male.  In  these  cases  we  recognize  at  once 
that  the  female  cells  are  distinguished  from  the  male  by  having 
two  accessory  chromosomes.  Wilson  was  able  to  demonstrate 
that  the  eggs  of  these  insects  always  contain  one  accessory 
chromosome.  When  such  an  egg  is  fertilized  by  a  spermato- 
zoon that  contains  an  accessory  chromosome,  then  the  egg 


FIG.  44.  FIG.  45. 

FIG.  44. — Protenor  belfragei.  Photogram  of  a  group  of  young  spermatozoa  with 
and  without  the  accessory  chromosome.  (See  text.) 

FIG.  45. — Alydus  pilosulus.  Second  division  of  the  spermatocyte.  The  acces- 
sory chromosome  lies  separated  from  the  others,  does  not  divide,  and  is  going  toward 
one  of  the  poles. 

develops  with  two  accessory  chromosomes  in  its  nucleus,  and 
there  arises  a  female,  but  if  such  an  egg  is  fertilized  by  a  sper- 
matozoon that  contains  no  accessory  chromosome  then  a  male 
is  produced.  Fig.  43  is  a  somewhat  incomplete  picture,  but 
shows  clearly  that  during  the  second  division  the  accessory 
chromosome  has  migrated  undivided  toward  one  pole.  An 
extremely  interesting  photograph,  Fig.  44,  shows  a  group  of 
spermatozoa.  The  so-called  heads  are  circular.  Half  of 


THE   DETERMINATION    OF    SEX 


97 


them  contain  a  still  distinct  accessory  chromosome,  which  in 
the  other  half  of  the  heads  cannot  be  seen.  This  picture 
affords  unquestionable  proof  that  there  really  are  two  kinds 
of  spermatozoa.  The  next  picture,  Fig.  45,  is  from  Alydus, 
and  demonstrates  to  us  again  the  second  division  and  the 
wandering  of  the  accessory  chromosome.  Next  follows  a 
drawing  of  Pyrrochoris,  Fig.  46,  which  represents  the  second 


V.V 

FIG.  46.  FIG.  47. 

FIG.  46. — Pyrrochoris   apterus.     Division  of   the 
second  spermatocyte. 

FIG.  47. — Anasa  tristis.      6  Two  views  of  dividing 
female  nuclei  (oogonia).  -*— 

FIG.  48. — Anasa    tristis.      6  The  second  spermatocyte  division.     The 
chromosome  is  lodged  at  one  pole  and  is  lacking  at  the  other. 


FIG.  48. 


accessory 


division  almost  completed.  Both  cells  are  clearly  recogniz- 
able, but  only  one  of  them  contains  an  accessory  chromosome. 
Next  follows  a  drawing  from  Anasa,  Fig.  47,  which  is  shown 
because  it  presents  to  us  two  views  of  the  cell  division.  In 
the  upper  cell  we  have  a  side  view  of  the  spindle,  and  we  notice 
at  once  the  so-called  equatorial  plate  which  is  formed  by  the 
collocation  of  all  the  chromosomes  in  the  equatorial  plane. 
The  lower  cell  is  a  view  of  an  equatorial  plate  seen  from  the 
spindle  pole.  Next  comes  a  picture  from  Anasa,  Fig.  48, 
which  shows  us  the  second  division  nearly  completed.  The 
wandering  of  the  accessory  chromosome  is  very  clear.  We 
pass  now  to  the  consideration  of  Galgulus,  Fig.  49.  The 


98 


THE   DETERMINATION   OF    SEX 


picture  shows  us  a  polar  view  of  an  equatorial  plate  of  the 
second  division.  The  ordinary  chromosomes  form  a  circle; 
in  the  center  we  see  the  accessory  chromosome,  which  in  this 
genus  is  not  simple  but  quadripartite.  Fig.  50  is  a  drawing 
from  Syromastes,  offering  a  polar  view  of  the  first  division. 
Wilson  discovered  in  this  genus  a  double  accessory  chromo- 
some which  does  not  lie  in  the  center  of  the  equatorial  plate 
but  outside  the  circle  of  the  remaining  chromosomes.  Quite 
similar  is  the  last  photograph  of  our  series,  Fig.  51,  which  is 


FIG.  49.  FIG.  50.  FIG.  51. 

FIG.  49. — Galgulus  oculatus.  Polar  view  ofAthe  equatorial  plate  of  the  second 
spermatocyte  division.  The  accessory  chromosome  is  quadripartite,  and  lies  in  the 
center. 

FIG.  50. — Syromastes  marginatus.  First  spermatocyte  division.  The  accessory 
chromosome  is  bipartite  and  lies  peripherally. 

FIG.  51. — Metapodius  terminalis.  First  spermatocyte  division.  The  accessory 
chromosome  lies  peripherally,  and  alongside  it  is  a  Y-chromosome. 

taken  from  Metapodius.  In  this  case  the  accessory  chromo- 
some is  simple  and  lies  outside,  while  near  it  occurs  a  Y- 
chromosome  which  is  very  similar  in  appearance  to  the  acces- 
sory, but  differs  from  it  in  its  further  development.  In  the 
center  of  the  equatorial  plate  lies  a  minute  chromosome,  the 
meaning  and  history  of  which  is  not  yet  completely  cleared  up. 
The  photographs  from  which  these  drawings  were  made  are 
very  beautiful  and  render  the  relations  perfectly  clear. 

Miss  Stevens  was  a  gifted  and  eager  investigator,  whose 
early  death  brings  a  heavy  loss.     In  the  year  1911,  she  pub- 


THE    DETERMINATION    OF    SEX 


99 


lished  the  discovery  of  an  accessory  chromosome  in  the  guinea- 
pig.47  Her  pictures  are  reproduced  in  Fig.  52,  and  show  the 
unquestionable  accessory  chromosome  indicated  by  the  letter 
x.  Guyer,48  also  an  American,  has  described  the  accessory 


FIG.  52. — Guinea-pig.  Spermatocyte  nucleus  in  the  preparatory  stage  (imme- 
diately after  the  synizesis),  in  which  the  accessory  chromosome  becomes  distinct. — 
After  Miss  Stevens. 

chromosome  in  birds  and  in  man,  and  it  has  been  found  in 
other  animals  also. 

That  the  spermatozoa  really  determine  sex  has  been  con- 
firmed by  a  capital  investigation  of  T.  H.  Morgan.49  Phyl- 
loxera"and  Aphis  lay  eggs  which  develop  parthenogenetically. 


FIG.  53. — The  unequal  spermatocyte  division,     a-c,  in  Phylloxera;  d-f,  in  Aphis 
solicola. — After  T.  H.  Morgan. 

After  several  generations,  and  under  conditions  which  are  in 
part  known  to  us,  the  females  deposit  eggs,  which  are  fertil- 
ized. All  fertilized  eggs  develop  into  females.  This  phenom- 
enon does  not  contradict  the  new  doctrine  of  sex  determina- 


TOO  THE   DETERMINATION    OF    SEX 

tion,  but  on  the  contrary  agrees  with  it  fully.  Morgan  dis- 
covered that  when  the  sexual  cells  in  the  male  develop  in  order 
to  produce  spermatozoa,  they  form  at  their  second  division 
two  elements  of  unequal  size.  Fig.  53  reproduces  two  series 
or  Morgan's  original  pictures.  In  the  first  series,  a-c,  and 
also  in  the  second,  d-f,  the  peculiar  division  is  represented. 
The  big  accessory  chromosome  moves  into  the  larger  of  the 
two  elements,  whech  then  develops  further  and  becomes  a 
spermatozoon.  The  small  element,  meanwhile,  shrivels  up. 
Thus  there  arise  in  these  animals  only  spermatozoa  with  the 
extra  chromosome,  and  accordingly  the  fertilized  ova  become 
females. 

American  investigations,  both  those  mentioned  and  others 
related  to  them,  lead  us  to  the  conclusion  that  sex  is  determined 
by  peculiarities  of  the  cells,  and  not  by  external  conditions. 
If  an  external  factor  influences  the  proportion  of  the  sexes, 
this  must  happen,  according  to  our  new  interpretation,  by 
interfering  with  the  development  of  one  or  the  other  sex.  In 
the  case  of  hermaphrodites,  interference  may  act  by  favoring 
the  transformation  of  indifferent  germ  cells  in  one  direction  or 
another. 

That  the  determination  of  sex  dwells  in  the  cells  is  made 
probable  also  by  the  phenomenon  of  polyembryony.  We 
have  already  learned  that  four  embryos  arise  from  a  single 
Armadillo  egg.  They  are  always  of  the  same  sex.  So  also 
in  the  case  of  small  insects,  the  parasitic  Chalcidae.  Accord- 
ing to  the  investigations  of  Bugnion,  Marshall  and  Silvester, 
many  embryos  arise  from  each  single  egg,  and  they  are  all  of 
the  same  sex.  We  can  explain  this  wonderful  phenomenon 
only  by  the  assumption  that  the  sex  of  the  egg  is  determined 
from  the  start. 

It  must  be  mentioned  that,  according  to  the  investigations 


THE   DETERMINATION   OF    SEX  IOI 

of  Baltzer,  the  sex  of  Echini  is  determined  not  by  the  spermato- 
zoa but  by  the  egg.  According  to  him,  the  Echini  have  two 
kinds  of  eggs  which  differ  in  their  chromosome  relations. 

The  investigation  of  the  determination  of  sex  must  be 
pursued  much  further.  It  is  above  all  important  to  ascertain 
whether  the  conditions  which  have  been  discovered  in  insects 
recur  in  all  animals  and  plants.  We  ask  at  the  same  time, 
what  are  the  relations  in  hermaphrodites?  We  cannot  at 
present  even  guess  the  answer  to  this  question. 

It  must  also  be  distinctly  emphasized  that  the  causal 
relations  are  not  clear.  We  have  learned  through  the 
memoirs  which  have  been  cited  that  the  nuclei  of  a  female  in 
a  considerable  number  of  animal  species  contain  more  chroma- 
tine  than  the  nuclei  of  a  male.  We  are  unable,  however,  to 
bring  this  peculiarity  into  causal  relation  with  the  difference 
of  sex.  It  is  quite  possible  that  the  excess  of  chromatine  is 
only  the  expression  of  more  essential  peculiarities,  although 
the  greater  probability  remains  that  the  accessory  chromo- 
some is  the  material  cause  and  basis  of  sex. 

Mortiz  Nussbaum  considered  the  two  sexual  elements  as 
homologous.  He  wrote  in  1880:  "Es  treten  somit  bei  der 
Befruchtung  nicht  zwei  heterogene  Elemente  zusammen,  die 

einander   erganzen  und es  treffen  sich  vielmehr 

zwei  homologe  Zellen,  von  denen  die  eine  zum  Zweck  der 
^Conjugation  sich  in  eine  beweglichere  Form  umgegossen  hat." 
The  homology  of  the  mature  ovum  with  a  spermatozoon  has 
been  generally  accepted.  The  new  investigations  make  this 
doubtful. 

We  know  at  present  four  different  species  or  types  of  cells. 
Two  types  are  diploid,  that  is  to  say,  they  have  the  full  num- 
ber of  chromosomes;  and  two  types  are  haploid,  that  is  to 
say,  they  possess  the  reduced  number  of  chromosomes. 


102  THE    DETERMINATION    OF    SEX 

A.  Diploid  cells. 

1.  Cells  of  the  female  bcdy. 

2.  Cells  of  the  male  body. 

B.  Haploid  cells. 

3.  The  female  elements   (mature    ova    and    polar 
globules) 

4.  The  male  elements  (spermatozoa). 

We  suspect  besides  that  there  is  a  fifth  kind  of  cell,  the 
indifferent,  which  we  shall  perhaps  later  learn  to  recognize 
in  hermaphrodites  and  lower  organisms. 

Thus  we  reach  the  conclusion  of  to-day's  lecture.  We 
advance  the  hypothesis  that  sex  rests  upon  a  physical  basis, 
which  we  recognize  by  differences  in  the  proportion  of  chro- 
matin  in  the  cells  of  the  male  and  female  body.  The  epoch- 
making  discoveries  of  my  American  colleagues  awake  joyful 
excitement  among  biologists.  We  are  pupils  of  German 
science,  and  in  carrying  out  the  investigations,  the  results  of 
which  I  have  presented  to  you  today,  our  investigators  have 
striven  to  equal  the  German  ideal.  May  our  activity  express 
to  you  our  gratitude ! 


VI. 
THE  SCIENTIFIC  CONCEPTION  OF  LIFE. 

Your  Excellencies! 

Biology  is  the  supreme  science  from  which  we  still  await 
the  solution  of  very  many  problems.  Unfortunately,  biology 
has  not  yet  become  a  united  science,  but  consists  of  sundry 
disciplines  more  or  less  separated  from  one  another.  The 
number  of  species  of  living  beings  is  enormous,  so  that  it  is 
impossible  for  a  single  investigator  to  become  familiar  with  all 
the  phenomena.  According  to  a  recent  estimate  of  Pratt,50 
published  in  1911,  the  number  of  known  animal  species  is 
522,400.  The  number  of  species  yet  to  be  described  is  cer- 
tainly also  very  great,  and  we  have  further  to  reckon  with  the 
considerable,  though  smaller,  number  of  species  of  plants. 

We  all  know  that  there  are  two  chief  types  of  naturalists: 
first,  of  those  who  incline  to  observation;  and  second,  of  those 
who  incline  to  experiments.  It  occurs  very  exceptionally  only 
that  a  naturalist  is  gifted  equally  in  both  directions,  and  hence 
we  see  that  biologists  for  the  most  part  are  either  morpholo- 
gists  or  physiologists.  We  divide  up  biology  into  single 
sciences  merely  to  adapt  it  to  the  capacity  of  the  individual. 
An  able  savant  may  perhaps  be  a  zoologist,  an  embryologist, 
a  biological  chemist,  a  physiologist,  or  a  paleontologist,  but 
he  cannot  be  a  real  biologist.  We  can  expect  only  from  the 
future  such  a  fusion  of  the  results  of  our  many  and  many- 
sided  biological  investigations  as  will  create  a  true  and  real 
biology.  To  attain  this  result  the  work  of  many  men  will  be 

103 


104  THE    CONCEPTION    OF    LIFE 

necessary  through  many  years.  The  contribution  of  any  one 
man  will  always  be  very  modest  in  comparison  with  the  whole 
task,  but  we  shall  certainly  succeed  by  our  united  efforts  in 
collecting  so  many  generalizations  that  we  shall  ultimately 
possess  a  unified  biological  science  which  will  have  a  much 
higher  and  farther-reaching  significance  for  us  than  our  present 
biology,  which  consists  of  single  sciences  imperfectly  fused. 
This  more  complete  biology  of  the  future  will  I  believe  be 
recognized  by  all  as  the  supreme  science.  We  foresee  that  it 
will  answer  many  questions  which  philosopher  shave  striven  for 
thousands  of  years  to  solve.  Philosophy,  strictly  speaking, 
is  occupied  chiefly  with  biological  phenomena.  Conscious- 
ness, the  relation  of  the  soul  to  the  body,  the  origin  of  reason, 
the  relations  of  the  external  world  to  psychical  perception,  and 
most  subjects  of  philosophical  thought  are  fundamentally 
biological  phenomena  which  the  naturalist  investigates  and 
analyzes.  If  these  fundamental  problems  of  human  thought 
are  ever  to  be  solved,  the  solution  will  be  presented  to  us, 
according  to  my  conviction,  not  by  philosophers,  but  by  natur- 
alists. I  can  express  my  thought  better  perhaps  by  saying 
that  the  future  fusion  of  philosophy  and  biology,  or  the 
inclusion  of  philosophy  in  biology,  is  to  be  expected.  His- 
torically, there  is  a  deep  cleft  between  philosophers  and 
naturalists.  The  philosopher  takes  existing  knowledge,  med- 
itates upon  it,  and  endeavors  by  deep  thought  to  draw  from 
his  knowledge  for  his  own  satisfaction  the  longed  for  gen- 
eral conceptions.  The  naturalist,  on  the  contrary,  strives 
to  widen  his  knowledge,  and  to  make  new  observations. 
He  wishes  to  increase  the  number  of  known  facts,  being  con- 
trolled by  the  conviction  that  the  generalizations  will  follow 
upon  the  increased  acquaintance  with  facts.  For  both  the 
philosopher  and  the  biologist  the  final  goal  is  the  same,  for 


THE    CONCEPTION    OF    LIFE  105 

both  desire  to  win  their  generalizations.  The  philosopher 
suffers  from  the  disadvantage  that  he  would  like  to  have  a 
complete  system,  a  coordinate  and  harmonious  explanation 
of  all  existence.  The  naturalist  desires  this  also,  but  he  has 
more  patience  and  does  not  expect  to  reach  his  goal  so 
quickly,  but  rejoices  every  time  that  he  advances  a  small 
distance  and  is  able  so  to  order  the  facts  known  to  him  that 
he  can  deduce  a  natural  law.  The  naturalist  utilizes  hypothe- 
ses as  much  as  the  philosopher.  The  naturalist's  hypothesis 
is  not  intended  to  complete  a  system  of  thought,  but  merely  to 
indicate  a  way  by  following  which  he  may  discover  facts  as 
yet  unknown.  During  our  present  debate  it  is  very  important 
not  to  forget  the  differences  between  philosophical  thinking 
and  scientific  investigation.  As  you  might  anticipate,  I  hold 
the  scientific  method  to  be  the  better  and  more  certain,  and 
therefore  cherish,  as  stated,  the  opinion  that  the  solution 
of  the  great  problems  of  human  existence,  if  it  is  ever  achieved 
by  us,  will  be  accomplished  through  biology. 

The  conception  of  life  is  very  uncertain,  but  we  are  able 
to  place  certain  foundation  stones  for  the  erection  of  this 
conception.  In  other  words,  biology  has  already  achieved 
some  important  generalizations,  several  of  which  have  been 
mentioned  in  the  previous  lectures. 

At  the  start,  emphasis  must  be  laid  on  the  fact  that  life 
is  known  to  us  only  bound  to  matter.  Only  through  matter 
can  life  express  itself,  only  through  matter  act  upon  the  world, 
and  only  through  matter  be  influenced  by  the  world.  As 
we  heard  in  the  first  lecture,  the  minimal  amount  of  living 
substance,  which  makes  life  possible,  is  relatively  great,  and 
probably  so  great  that  we  can  see  it  with  the  microscope. 
I  at  least  regard  it  as  improbable  that  there  are  invisible 
living  beings. 


106  THE   CONCEPTION   OF   LIFE 

The  opinion  is  widespread  in  unscientific  circles  that 
life  may  occur  without  a  material  basis.  We  encounter  this 
opinion  in  almost  all  religions,  for  they  teach  the  survival  of 
the  soul,  at  least  of  man.  In  recent  years  repeated  attempts 
have  been  made  to  prove  these  religious  doctrines  scientific- 
ally. Thus,  the  spiritualists  assert  that  they  can  demonstrate 
the  existence  of  living  men  without  material  bodies.  It  may 
be  asserted  without  overventuring  that  the  majority  of  biolo- 
gists do  not  consider  this  spiritualistic  demonstration  as  sound. 
Exceptions  are  rare.  The  most  famous  of  such  exceptions  is 
Alfred  Wallace,  co-founder  with  Darwin  of  the  theory  of 
natural  selection.  He  remains  even  in  his  extreme  old  age  an 
eager  follower  of  spiritualism.  I  have  conversed  with  him 
a  few  times  on  the  subject,  and  got  the  impression  that  he 
keeps  the  whole  field  of  spiritualism  separated  from  science, 
and  that  he  completely  sets  aside  in  the  discussion  of  spiritual- 
ism those  criteria  which  he  would  inevitably  put  up  in  the 
case  of  scientific  investigation.  No  impression  was  made 
upon  him  by  the  numerous  instances  in  which  it  had  been 
proven  that  alleged  spiritualistic  phenomena  were  due  to 
cheating.  He  demanded  that  cheating  should  be  proved  in 
every  case  before  he  could  yield  his  faith.  Is  not  the  whole 
doctrine  of  the  spiritualists,  properly  speaking,  a  psychical 
phenomenon,  which  we  are  not  to  attempt  to  explain  as  a  real 
phenomenon  of  the  outer  world? 

There  has  been  founded  in  England  a  society  for  psychical 
research.  This  society  includes  among  its  members  men  of 
good  standing,  who  have  carried  on  very  serious  investiga- 
tions. The  formation  of  the  society  was  a  consequence  of 
observations  made  in  Cambridge,  from  which  the  conclusion 
was  drawn  that  men  may  communicate  with  one  another 
directly  without  using  the  means  previously  known  to  us. 


THE    CONCEPTION   OP    LIFE  1 07 

This  mode  of  communication  was  named  telepathy.  When 
the  British  Association  for  the  Advancement  of  Science  held 
its  meeting  in  Montreal  (1886),  I  made  the  acquaintance  of 
several  of  the  leaders  of  this  Society.  At  that  time  it  seemed 
possible  that  telepathy  was  a  real  phenomenon,  and  therefore 
in  response  to  the  suggestions  of  these  gentlemen  we  founded 
a  society  for  psychical  research  in  America.  After  a  number 
of  years,  the  scientific  men  who  had  founded  the  American 
society  withdrew,  in  part  because  it  was  found  out  that  the 
alleged  phenomena  of  telepathy,  which  were  first  described, 
were  produced  by  cheating.  The  English  society  is  still 
active,  and  now  defends  the  doctrine  that  vital  phenomena 
may  occur  without  the  usual  material  body,  and  that  it  is 
possible  to  enter  into  communication  with  the  spirits  of  the 
dead,  although  only  under  conditions  which  occur  rarely. 
If  this  doctrine  could  be  scientifically  assured,  it  would  con- 
stitute the  greatest  discovery  of  our  time.  The  demonstra- 
tion is,  however,  little  convincing.  In  Germany,  so  far  as  I 
know,  psychical  research  has  received  little  attention.  In 
England  and  America  one  hears  and  reads  much  about  it. 
Of  course,  we  cannot  assert  a  priori  that  survival,  in  the  sense 
indicated  above,  is  impossible,  yet  the  biologist  is  likely  to 
stick  to  his  assertion  that  the  presence  of  the  material  basis  is 
the  exclusive  substratum  for  life. 

Where  does  the  living  substance  come  from?  So  far  as 
we  know  at  present  it  arises  only  from  itself,  it  propa- 
gates itself,  and  can  be  created  only  by  itself.  If  it  should 
once  be  entirely  destroyed,  life  on  our  earth  would  cease. 
Formerly  this  view  did  not  prevail,  for  it  was  believed  that 
spontaneous  generation  occurred  in  the  world.  In  mediaeval 
times  learned  men  adhered  contentedly  to  the  idea  that  the 
insects  which  appear  in  decaying  meat  arise  by  spontaneous 


08  THE    CONCEPTION    OF    LIFE 

generation  from  the  meat.  Francesco  Redi's  famous  experi- 
ments brought  the  first  proof  that  the  insects  arise  only  when 
insect  eggs  are  laid  in  the  meat.  For  a  still  longer  time  it 
was  considered  possible  that  the  simplest  organisms,  bacteria, 
etc.,  could  be  formed  by  spontaneous  generation.  The 
experiments  of  Pasteur,  made  not  many  years  ago,  brought 
the  final  proof  that  this  also  is  impossible.  On  Pasteur's 
discovery  is  based  the  antiseptic  treatment  of  the  surgeon, 
which  has  for  its  object  simply  to  prevent  the  entrance  of  the 
microscopic  germs  which  cause  sepsis.  We  must  regard  it 
as  an  assured  conclusion  of  biology  that  spontaneous  genera- 
tion has  never  been  observed,  and  many  naturalists  incline 
to  assert  that  it  never  will  be  observed  by  us. 

Thus  we  come  back  to  the  question,  where  does  the  living 
substance  come  from?  Helmholtz51  and,  following  him, 
Arrhenius  have  defended  a  hypothesis  according  to  which 
life  reached  this  earth  from  outside.  This  hypothesis  assumes 
the  occurrence  of  very  small  living  germs,  about  of  the  size  of 
the  smallest  individual  germs  known  to  us  as  occurring  on  the 
earth,  which  are  driven  hither  and  thither  in  space,  and  may 
accidentally  hit  the  earth,  or  which  perhaps  are  brought  on 
meteorites,  or,  according  to  the  hypothesis  advanced  by 
Arrhenius,  by  the  beats  of  waves  of  light.  The  hypothesis  is 
bold  and  interesting.  If  it  is  correct,  the  possibility  exists 
of  our  receiving  organisms  which  differ  from  all  species  hith- 
erto occurring  on  the  earth,  and  which  therefore  might  initiate 
a  new  evolution  of  living  beings.  But  even  if  we  assume  the 
correctness  of  this  hypothesis,  it  still  offers  no  answer  to  our 
question,  because  it  assumes  the  previous  existence  of  living 
substance.  Alongside  this  theory  occurs  a  new  hypothesis  of 
spontaneous  generation.  This  second  hypothesis  is,  so  to 
speak,  a  side  product  of  the  doctrine  of  evolution.  After  the 


THE    CONCEPTION    OF   LIFE  1 09 

astronomers  had  asserted  the  evolution  of  our  planetary 
system,  after  the  geologists  had  asserted  the  evolution  of  the 
world,  followed  Darwin,  who  convinced  us  of  the  necessity  of 
assuming  the  evolution  of  plants  and  animals.  Evolution 
leads  us  back  to  a  time  when  the  conditions  on  our  earth  were 
such  that  life,  as  we  now  know  it,  must  have  been  impossible. 
Life  appeared  later.  It  is  therefore  clear  that  somehow  living 
substance  must  have  arisen  on  the  earth.  Thus  it  became  an 
intellectual  necessity  for  us  to  assume  in  this  sense  the  spon- 
taneous generation  of  life.  Those  who  make  this  assumption 
have,  strictly  speaking,  only  one  explanation  to  offer,  namely 
the  supposition  that  proteid  molecules  could  be  formed,  under 
the  then  prevailing  conditions,  and  by  chance  so  come  together 
and  unite  in  combination  with  other  substances  that  they 
would  produce  the  first  living  substance.  If  we  may  venture 
to  pass  judgment  on  this  hypothesis  we  must  bear  in  mind 
that  it  is  merely  the  expression  of  our  desire  to  meet  the 
assumed  needs  of  the  doctrine  of  evolution.  The  hypothesis 
has  no  further  real  scientific  foundation.  Pfliiger52  has 
endeavored  in  a  clever  and  interesting  memoir  to  determine 
speculatively  the  possibility  of  the  origin  of  proteid  sub- 
stances, but  he  did  not  get  beyond  speculation.  To  be  exact, 
we  must  consider  that  we  have  reached  the  new  doctrine  of 
spontaneous  generation  through  our  inability  to  conceive  the 
origin  of  life  otherwise.  I  imagine  a  very  interesting  and 
instructive  book,  which  is  to  be  on  the  theme  how  often  the 
scientific  man  has  been  led  to  false  conclusions  through  the 
assumption  "it  must  be  so  because  we  cannot  conceive  it 
otherwise."  We  may  never  say  in  science,  it  is  impossible. 
The  time  of  scientific  surprises  is  not  over.  A  few  years  ago, 
physicists  thought  that  they  had  already  discovered  the  basic 
phenomena  of  their  science,  and  yet  they  are  all  today  occu- 


110  THE    CONCEPTION   OF   LIFE 

pied  with  so  transforming  their  Tundamental  conceptions 
that  they  will  correspond  to  the  discoveries  of  recent  years. 
Some  surprises  will  surely  come  in  biology,  and  therefore  I 
prefer  to  take  an  agnostic  position  in  regard  to  the  doctrine  of 
spontaneous  generation,  and  to  cling  to  the  possibility  that  the 
final  explanation  will  be  found  in  some  unexpected  direction, 
or  will  be  given  by  some  phenomenon  as  yet  wholly  unknown 
to  us.  It  is  much  achieved  that  we  can  now  maintain  the 
statement  that  protoplasm,  under  which  term  we  include  the 
nucleus,  is  the  physical  basis  of  life. 

Let  us  now  pass  to  the  consideration  of  the  general  activity 
of  protoplasm.  First  of  all,  we  must  regard  metabolism  which 
we  must  look  upon  as  the  basic  phenomenon  of  life.  Very 
many  chemical  substances  are  taken  up  by  protoplasm  which 
in  part  are  worked  over  into  new  chemical  combinations,  by 
which  the  growth  of  the  living  substance  is  made  possible,  and 
at  the  same  time  the  necessary  material  is  produced  for  the 
performance  of  work.  In  consequence  of  the  performance  of 
work  simple  chemical  compounds  arise  which  cannot  be  fur- 
ther used  by  the  protoplasm,  and  are  therefore  discarded,  and 
are  designated  by  us  as  excretes.  In  order  to  maintain  life, 
the  stream  of  matter  through  the  protoplasm  must  continue. 
We  have  no  occasion  to  assume  that  metabolism  is  more  than 
a  series  of  chemical  processes. 

By  nourishing  itself,  protoplasm  grows,  and  as  a  conse- 
quence thereof  follows  the  multiplication  or  proliferation  of 
cells.  We  know  also  that  when  protoplasm  grows,  the  new 
formed  protoplasm  is  similar  to  that  already  present.  The 
self-maintenance  of  its  own  peculiarities  is  highly  character- 
istic of  protoplasm  and  we  recognize  in  this  peculiarity  the 
basis  of  heredity.  The  question  of  variations  is  a  very  differ- 
ent one.  The  doctrine  of  evolution  forces  us  to  the  assump- 


THE    CONCEPTION    OF   LIFE  III 

tion  that  protoplasm,  in  spite  of  the  fact  that  so  far  as  we  can 
observe  it  propagates  itself  and  in  this  propagation  remains 
like  itself,  nevertheless  alters  in  the  course  of  time.  The 
continuous,  slowly  progressive  change  of  protoplasm  which 
has  led  to  the  origin  of  species,  we  designate  as  the  phylogen- 
etic  variation.  Many  experiments  on  variation  have  been 
made  in  recent  years.  In  one  direction  our  knowledge  has 
been  greatly  extended.  The  so-called  Mendelian  variation 
is  certainly  known  to  you.  It  is  remarkable  that  the  varia- 
tions which  have  been  found  in  the  investigation  of  the  Men- 
delian law  are  not  new  variations,  but  on  the  contrary  in 
such  cases  as  have  hitherto  been  analyzed  with  certainty,  we 
have  to  do  with  the  dropping  out  of  a  character.  This  is 
illustrated  by  the  beautiful  experiments  of  Professor  Morgan53 
of  Columbia  University  on  Drosophila.  The  eyes  of  this 
small  fly  vary  in  their  color.  Morgan  has  succeeded  in  prov- 
ing by  his  experiments  that  four  factors  determine  the  color 
of  the  eye,  and  that  all  variations  in  the  color  are  caused  by 
the  dropping  out  of  one  or  more  of  these  factors.  The  varia- 
tions arise  by  the  exclusion  of  a  character  which  is  present  in 
normal  individuals.  We  still  have  to  discover  the  origin  of 
new  variations,  although  we  have  already  some  indications  of 
the  answer  to  this  problem.  I  should  like  to  discuss  the  mat- 
ter if  time  permitted,  but  I  must  restrict  myself  to  a  single 
example.  Professor  Stockard54  has  made  experiments  at  the 
Biological  Station  at  Woods  Hole,  which  led  him  to  the  fine 
discovery  that  the  addition  of  minute  quantities  of  magnesium 
chloride  to  ordinary  sea  water  creates  some  wonderful  modi- 
fications in  the  development  of  bony  fishes.  He  employed 
for  his  experiments  Fundulus  heteroclitus,  a  species  of  minnow 
very  common  at  Woods  Hole.  Eggs  which  are  kept  in  the 
magnesium  water  produce  embryos  which  appear  normal  in 


112  THE    CONCEPTION    OF   LIFE 

most  respects.  They  show,  however,  a  tendency  toward 
fusion,  in  the  median  line,  of  the  two  eyes  which  normally  are 
lateral.  The  fusion  may  go  so  far  that  a  fish  is  produced 
which  has  only  one  eye  in  the  median  line  of  the  head.  Such 
an  embryo  is  called  a  Cyclops.  It  is  thus  shown  that  an  alter- 
ation in  the  chemical  conditions  produces  an  extraordinary 
alteration  of  the  development.  In  this  connection  we  may 
mention  also  the  interesting  discovery  of  artificial  parthen- 
ogenesis by  A.  D.  Mead,20  which  has  been  confirmed  by 
Loeb,56  Matthews55  and  others.  These  investigators  have 
demonstrated  that  eggs  may  be  excited  to  further  develop- 
ment through  various  chemical  means  without  being  fertil- 
ized in  the  normal  manner.  An  egg  which  has  remained 
unfertilized  and  does  not  receive  the  chemical  excitation  will 
break  down.  The  fate  of  the  egg  may  be  completely  altered 
by  a  relatively  small  chemical  treatment.  In  all  these  cases 
we  must  ascribe  the  striking  alterations  of  the  vital  processes 
to  chemical  action. 

The  immediate  microscopic  observation  of  cells  during  their 
physiological  activity  teaches  us  that  the  phenomena  of 
life  depend  upon  their  material  substratum.  We  know,  for 
example,  in  muscles,  which  have  been  recently  carefully  inves- 
tigated by  Meigs,57  very  instructive  relations.  There  are 
two  kinds  of  muscle  fibers,  the  so-called  smooth  and  the  stri- 
ated. The  smooth  muscles  occur  chiefly  in  the  internal 
organs.  When  they  contract  they  give  off  water  which  may 
be  found  between  the  single  fibers.  When  they  expand  they 
take  up  the  water  again.  The  striated  muscles  are  for  the 
most  part  connected  with  the  skeleton.  Their  fibers  are  much 
larger  than  the  smooth  muscle  fibers,  and  have  in  their  interior 
very  fine  contractile  fibrils,  Fig.  9,  which  I  have  already  had 
occasion  to  mention.  When  the  striated  muscles  contract, 


THE    CONCEPTION    OF    LIFE  113 

water  is  taken  up  by  the  fibrils,  to  be  given  up  by  them  again 
when  the  muscles  elongate.  The  movement  of  water  in  the 
two  types  occurs  in  opposite  senses  during  contraction.  In 
smooth  muscles  it  moves  out  from  the  fibers,  in  striated,  into 
the  fibrils.  Meigs'  investigation  was  carried  out  in  part  in 
my  laboratory,  and  I  have  been  able  to  confirm  his  results 
by  the  inspection  of  his  preparations.  The  contraction  of 
muscles  thus  appears  to  depend  on  the  movements  of  fluid 
within  the  muscle,  and  muscular  contraction  is  a  chemical- 
physical  phenomenon.  Nerve  cells  contain  in  their  ncrmal 
condition  small  mases,  commonly  designated  as  Nissl's  bodies. 
When  a  nerve  cell  functions  these  masses  are  used  up  during 
its  activity.  The  observations  of  C.  F.  Hodge58  of  Clarke 
University  are  very  convincing.  He  investigated  the  central 
nervous  system  of  swallows.  He  collected  some  birds  in  the 
morning  when  they  were  fresh,  and  again  others  at  the  end  of 
the  day  when  they  were  exhausted  by  many  hours  of  flight. 
He  found  it  easy  to  demonstrate  that  the  content  of  the  nerve 
cells  was  used  up  during  the  day,  and  that  the  exhausted 
cells  showed  clearly  the  loss  which  they  had  suffered.  He 
also  found  that  certain  nerve  cells  in  a  very  old  man  have  a 
permanently  exhausted  appearance  and  were  therefore  no 
longer  capable  of  functioning.  (Mention  should  be  added  of 
the  very  extensive  investigation  of  the  exhaustion  of  nerve 
cells  by  Dr.  Crile,  an  account  of  which  he  presented  to  the 
American  Philosophical  Society  in  April,  1913.)  When  we 
consider  that  our  highest  performances  are  functions  of  our 
nerve  cells,  we  must  admit  that  our  psychical  activity  also  de- 
pends upon  the  activity  and  the  using  up  of  living  substance. 
If  we  pass  to  the  organs  of  the  so-called  vegetative  life  we 
find  similar  conditions.  The  secretion  of  glands,  as  we  first 
learned  through  the  investigations  of  R.  Heidenhain,  is  formed 


114  THE    CONCEPTION    OF    LIFE 

usually  from  substances  which  we  can  easily  see  under  suitable 
conditions  in  the  gland  cells.  When  the  gland  functions, 
these  substances,  which  often  may  be  seen  as  granules  in 
the  protoplasm,  are  metamorphosed  chemically,  in  order  to 
form  the  secretion  which  is  given  off  by  the  gland.  Very 
exact  recent  investigations  of  these  processes  have  been  made 
by  the  American,  Bensley.59  As  we  heard  in  the  fifth  lecture, 
we  can  distinguish  in  the  nuclei  of  sexual  cells  in  many  animals 
a  so-called  chromosome  which  differs  from  the  remaining 
chromosomes.  It  claims  our  special  interest  because  it 
occurs  in  the  cells  of  the  female  body,  but  on  the  contrary  is 
not  found  in  the  cells  of  the  male  body;  hence,  as  we  heard, 
the  hypothesis  that  these  chromosomes  determine  the  sex. 
As  we  have  already  considered  these  relations,  it  will  suffice 
merely  to  mention  the  chromosomes.  In  conclusion  let  me 
again  direct  your  attention  to  the  fact  that  always  as  we 
grow  old  we  can  observe  visible  modifications  of  the  cells. 

The  phenomenon  of  metabolism  and  the  phenomenon  of 
the  visible  alterations  which  can  be  observed  in  cells,  lead  to 
the  conclusion  that  the  life  processes  are  explicable  by  the 
chemical  properties  and  the  structure  of  protoplasm  and 
nucleus. 

This  explanation  is  called  the  mechanistic  theory  of  life, 
and  has  found  acceptance  with  the  majority  of  biologists. 
It  cannot  be  doubted  that  the  mechanistic  explanation  is 
stringently  sufficient  for  most  vital  processes.  Whether  it  is 
sufficient  to  explain  all  the  phenomena  of  life  is  a  question 
in  regard  to  which  opinions  diverge.  On  one  side  there  are 
the  Monists  and  their  friends,  and  on  the  other  the  Vitalists 
and  Dualists.  There  are  biologists  who  make  a  dogma  of  the 
mechanistic  theory  and  defend  their  doctrine  with  a  vehe- 
mence which  recalls  the  theological  discussions  of  the  Middle 


THE    CONCEPTION   OF   LIFE  115 

Ages.  They  express  their  opinions  with  limitless  certainty 
and  listen  unwillingly  if  one  does  not  agree  with  them.  We, 
however,  must  consider  the  question  more  quietly  and  remain 
remote  from  over-eagerness,  and  this  chiefly  because  there 
are  important  vital  phenomena  known  to  us  which  up  to 
the  present  at  least  cannot  be  made  comprehensible  by  the 
mechanistic  theory. 

Of  such  phenomena  I  take  the  privilege  of  enumerating 
three : 

1.  Organization. 

2.  The  teleological  mechanism. 

3.  Consciousness. 

Organization  is  characteristic  of  life,  but  exactly  what 
the  organization  of  living  substance  is,  is  by  no  means  clear 
to  us.  We  have  already  discussed  this.  We  only  know 
that  organization  is  created  by  uniting  various  chemical 
substances,  some  of  which  form  small  masses  which  remain 
separate  from  one  another.  We  know  also  that  the  living 
substance  always  contains  in  solution  certain  salts.  Water 
is  of  course  indispensable.  We  possess  no  knowledge  how  this 
mixture  arises,  or  how  it  is  capable  of  maintaining  and  increas- 
ing itself.  We  may  indeed  say  that  we  must  assume  that  this 
organization  is  to  be  explained  mechanistically,  but  then  we 
really  merely  say  that  we  have  hit  on  no  better  explanation 
hitherto  and  that  properly  speaking  we  cannot  give  a  real 
explanation  at  all.  So  long  as  the  essence  of  organization  is 
completely  unknown,  we  must  refuse  with  decision  to  admit 
the  complete  sufficiency  of  the  mechanistic  theory. 

One  of  the  most  wonderful  properties  of  life  is  the  tele- 
ology, with  which  the  vital  functions  are  carried  out.  The 
changes  in  a  living  animal  or  in  a  living  plant  progress  as  if  the 


Il6  THE    CONCEPTION    OF    LIFE 

organism  was  working  conscious  oFIFs  aim.  How  did  this 
vital  teleology  arise;  how  has  it  maintained  itself?  That 
teleology  is  to  be  explained  by  the  mechanistic  theory  is 
again  an  assumption,  the  justification  of  which  we  still 
await. 

Consciousness  is  the  most  obscure  problem  of  biology. 
Hitherto,  the  philosophers,  and  more  recently,  the  psycholo- 
gists, but  not  the  biologists,  have  occupied  themselves  with 
the  study  of  consciousness,  and  they  have,  it  seems,  only  got 
so  far  that  they  can  make  it  clear  to  us  that  consciousnes  is 
an  ultimate  conception,  that  is  to  say,  a  conception  which 
cannot  be  further  analyzed.  In  an  address,60  which  I  delivered 
in  the  year  1902,  as  President  of  the  American  Association 
for  the  Advancement  of  Science,  I  endeavored  to  make  clear 
the  importance  of  consciousness  in  the  evolution  of  animals. 
I  adhere  today  to  the  opinion  then  expressed  that  the  phylo- 
genetic  development,  especially  of  vertebrates,  was  dominated 
by  the  evolution  of  consciousness.  If  this  is  the  case,  it  offers 
an  important  proof  of  the  great  importance  of  consciousness 
in  animal  life,  and  in  fact  we  are  forced  to  ascribe  to  conscious- 
ness the  leading  role  in  evolution.  It  can  have  importance 
only  if  it  influences  the  life  of  animals.  Consciousness  is 
active.  In  the  address  mentioned  above  I  stated  that  accord- 
ing to  my  conviction  it  is  impossible  to  avoid  the  conclusion 
that  consciousness  stands  in  immediate  causal  relation  to 
physiological  processes.  What  is  consciousness?  There  are 
so  far  as  I  know  only  three  possible  explanations  from 
which  we  must  choose.  According  to  one  view,  consciousness 
is  not  a  real  phenomenon,  but  a  so-called  epiphenomenon, 
something  that  accompanies  the  physiological  processes  with- 
out exerting  any  influence  upon  them.  As  a  celebrated  psy- 
chologist expressed  it  to  me,  consciousness  is  merely  the  other 


THE    CONCEPTION    OF   LIFE  1 17 

side  of  the  alterations  in  the  protoplasm  of  the  brain  cells. 
According  to  a  second  view,  consciousness  is  a  special  form  of 
energy.  This  view,  strictly  taken,  I  believe  to  be  purely 
metaphysical.  No  observations  or  experiments  are  known  to 
me  which  even  suggest  that  energy  can  be  transformed  into 
consciousness.  As  you  have  doubtless  already  perceived,  I  am 
not  inclined  to  regard  consciousness  as  a  condition  of  the  pro- 
toplasm or  as  a  form  of  energy.  If  we  admit,  as  according  to 
my  interpretation  we  must  admit,  that  consciousness  plays 
an  important  role  in  life,  then  it  must  be  able  to  act  in  some 
way  upon  the  body.  Such  an  action  can  reveal  itself  only  by 
the  transformation  of  energy  somewhere  in  the  body.  Thus 
we  are  led  directly  to  the  hypothesis  that  consciousness  may 
cause  the  transformation  of  energy,  and  that  it  is  itself  not 
energy. 

I  acknowledge  the  great  significance  and  importance  of 
the  mechanistic  theory  of  life.  A  pupil  of  CarlLudwig  may 
not  turn  away  from  this  theory,  for  it  has  proven  of  the 
highest  value  in  science,  and  has  guided  many  investigations 
to  fortunate  termination.  But  must  we  carry  our  enthusiasm 
for  this  view,  for  which  we  are  indebted  chiefly  to  the  great 
Leipzig  physiologist,  so  far  that  we  become  immediately 
converts  to  the  dogma  that  this  theory  suffices  for  all  the  phe- 
nomena of  life?  I  do  not  belong  to  those  who  wish  to  establish 
monism  as  the  definite  and  final  philosophy.  On  the  con- 
trary the  possibility  still  remains  that  we  must  accept  a  dual- 
istic  philosophy  as  the  desired  solution.  According  to  this 
philosophy  we  recognize  in  the  universe  energy  and  conscious- 
ness. We  biologists,  however,  are  not  philosophers.  We 
make  no  assumption  to  offer  you  final  explanations.  The 
conception  of  consciousness  which  I  have  laid  before  you  is 
not  a  philosophical  speculation,  but  a  scientific  hypothesis 


Il8  THE   CONCEPTION    OF   LIFE 

which  is  brought  forward  because  it  makes  the  totality  of 
vital  phenomena  more  comprehensible.  It  would  be  sup- 
remely interesting  to  know  and  we  hope  that  in  the  future  it 
will  be  known  what  consciousness  is.  But  the  first  question 
for  the  biologist  is:  Is  consciousness  a  true  cause? 

And  now  for  our  final  conclusion.  Life  is  bound  to  matter. 
Vital  phenomena  are  alterations  of  the  living  substance  which 
we  describe  by  saying  that  they  are  transformations  of  energy. 
But  there  always  remains  the  possibility  that  consciousness 
cannot  be  explained  mechanistically,  that  it  is  neither  a  con- 
dition of  protoplasm,  nor  a  special  form  of  energy,  but  some- 
thing of  its  own  kind,  not  comparable  with  anything  else 
that  we  know,  and  that  it  reveals  itself  by  causing  transforma- 
tions of  energy. 

There  still  remains  for  me  to  thank  you  for  the  attention 
with  which  you  have  honored  me,  and  for  the  extreme  hospi- 
tality which  I  have  enjoyed  here.  May  the  University  of 
Jena  grow  and  prosper!  Of  her  I  shall  carry  with  me  to  my 
distant  home  memories  to  which  I  shall  always  return  with 
joy  so  long  as  I  live.  To  her  I  say  farewell,  and  to  you,  thanks ! 


NOTES  IIQ 

NOTES. 

1.  Carl  Heitzmann,  Microscopical  morphology  of  the  animal  body  in  health 
and  disease.     8vo.  pp.,  xix,  849.     New  York,  1885.     F.  H.  Vail  and  Co. 

2.  C.  O.  Whitman,  The  inadequacy  of  the  cell  theory. 

3.  E.  B.  Wilson,  The  cell  in  development  and  inheritance.     Second  edition. 
New  York,  1900. 

4.  J.  Loeb,  Arch,  gesamt.  Physiol.,  1907,  Bd.  cxviii,  s.  7. 

5.  Ralph  L.  Lillie,  Certain  means  by  which  star-fish  eggs  naturally  resistant 
to  fertilization  may  be  rendered  normal  and  the  physiological  conditions 
of  this  action.     Biol.  Bulletin,  XXII,  328-346,  1911. 

6.  A.  C.  Eycleshymer,  The  cytoplasmic  and  nuclear  changes  in  the  striated 
muscle-cell  of  Necturus.     Amer.  Journ.  of  Anat.,  Ill,  285—310. 

7.  Professor  Whitman  made  extensive  experiments  concerning  heredity  in 
pigeons,  and  for  this  purpose  he  kept  a  large  flock  of  these  birds.     At  his 
invitation  several  students  availed  themselves  of  the  opportunity  to  make 
a  careful  study  of  the  early  development  of  pigeons.     The  resulting  stud- 
ies offer  us  by  far  the  most  exact  descriptions  of  the  early  development  of 
birds  which  we  possess.     Compare: 

E.  H.  Harper,  The  fertilization  and  early  development  of  the  pigeon's 
egg.  Amer.  Journ.  Anat.,  Ill,  349-386,  1904. 

Mary  Blount,  The  early  development  of  the  pigeon's  egg  with  especial 
reference  to  polyspermy.  Journ.  of  Morphol.,  XX,  1-64,  1909. 

J.  Thomas  Patterson,  GaStrulation  in  the  pigeon's  egg.  A  morpholog- 
ical and  experimental  study.  Journ.  of  Morphol.,  XX,  65-123,  1909. 

8.  R.   G.  Harrison  has  published  many  experiments  on  the  origin  of  nerve 
fibers: 

1901.     Arch.f.  mikrosk.  Anatomic,  Bd.  LVII,  354-444. 

1903.  Arch.  f.  mikrosk.  Anatomic,  Bd.  LXIII,  35-149. 

1904.  American  Journ.  of  Anatomy,  III,  197—220. 

1906.  American  Journ.  of  Anatomy,  V,  121-131. 

1907.  Journal  of  Experimental  Zoology,  IV,  230-281. 

1907.  Anatomical  Record,  No.  5. 

1908.  Anatomical  Record,  No.  8. 
1908.     Anatomical  Record,  II,  385-410. 

1910.     Arch.  f.  Entwicklungsmechanik,  XXX,  Tl.     11,15-33. 

1910.    The  outgrowth  of  the  nerve  fiber  as  a  mode  of  protoplasmic 

movement.     Journ.  Exp.  Zoology,  IX,  787-846. 

In  the  last-nientioned  article  he  describes  the  observations  made  upon 
in  vitro  cultures,  and  pictures  in  detail  the  outgrowth  of  the  axis-cylinders 
(nerve-fibers)  of  young  nerve  cells.  Harrison  has  definitely  solved  the 
problem  which  has  long  been  disputed. 


I 20  NOTES 

9.  C.  S.  Minot,  Age,  Growth,  and  Death,  p7~2bi,  where  the  literature  is  also 

given. 

TO.  V.  E.  Emmel,  A  study  of  the  regeneration  of  tissues  in  the  regenerating 
crustacean  limb.  Amer.  Journ.  Anat.,  X,  109-158. 

1 1.  As  far  as  I  know,  H.  Braus  was  the  first  to  graft  rudimentary  extremities. 
Compare  Verh.  Anat.  Ges.,  XVIII  and  Anat.  Anz.,  XXVI.     His  experi- 
ments have  been  repeated  and  extended  by  W.  H.  Lewis  and  R.  G. 
Harrison. 

12.  W.  H.  Lewis  and  Mrs.  Lewis  conjointly  have  made  experiments  upon 
the   in  vitro   cultures   of  embryonic  tissue.     Compare  The  Anatomical 
Record,  VI,  195  and  207. 

13.  Carl  Semper,  Die  Verwandtschaften  der  gegliederten  Tiere,  iii.     Sem- 
pers  Arbeiten.     Zool.  Zootom.  Institut  Wiirzburg,  Bd.  Ill,  115. 

14.  The  text  deals  with  the  law  of  genetic  restriction,  which  can  be  found 
more  definitely  stated  in  my  "Laboratory  Text-book  of  Embryology," 
2nd  ed.,  p.  14. 

T5.  E.  A.  Schafer,  Life:  its  nature,  origin  and  maintenance.  (Presidential 
Address  before  the  British  Association  for  the  Advancement  of  Science, 
Dundee,  September,  1912).  Longmans,  Green  &  Co.,  London,  1912. 

1 6.  W.  Kleinenberg,  The  development  of  the  earth-worm,  Lumbricus  trap- 
ezoides.     Quart.    Journal    of  Microsc.    Science,   XIX,    206-244,    1879. 
(Compare  also,  Zeitschr.  wiss.  Zool.,  XLIV,  1886.) 

17.  E.  B.  Wilson,  The  germ  bands  of  Lumbricus.     Journ.  of  Morphology, 
I,  p.  183. 

1 8.  J.  T.  Patterson,  A  preliminary  report  on  the  demonstration  of  poly- 
embryonic  development  in  the  Armadillo.     Anat.  Anzeiger,  XLI,  369- 
381.     (Cites  also  the  earlier  works  of  Newman  and  Patterson,  et  al.) 

19.  Hans  Driesch,  Entwicklungsmechanische  Studien  I.     Zeitschr.  f.  wiss. 
Zoologie,  LIII,  1 60. 

20.  A.  D.  Mead,  Biological  Lectures  at  Woods  Hole,  Boston,  1898. 

21.  F.  A.  Woods,  Origin  and  Migration  of  the  germ-cells  in  Acanthias. 
American  Journ.  of  Anat.,  I,  307.     (The  so-called  "precocious  segrega- 
tion" of  the  sexual  cells  of  fishes  was  first  more  exactly  described  by  C. 
H.  Eigenmann.) 

22.  B.  M.  Allen  has  determined  the  history  of  the  sexual  cells  in  four  verte- 
brate types. 

"    1911.     Amia,  Journal  of  Morphology,  XXII,  p.  n. 
1911.    Lepidosteus  Journal  of  Morphology,  XXII,  p.  2, 
1907.     Rana,  Anat.  Anzeiger,  XXX,  339. 
1906.     Chrysemys,  Anat.  Anzeiger,  XXIX,  217. 

23.  R.  W.  Hegner,  The  origin  and  early  history  of  the  germ-cells  in  some 
Chrysomelid  beetles.     Journal  of  Morphology,  XX,  231-296,  4  Taf.,  1909. 


NOTES  121 

24.  Oskar  Hertwig,  Beitrage  zur  Kenntnis  der  Bildung,  Befruchtung  und 
Teilung  des  tierischen  Eies.     Morphol.  Jahrb.,  I,  III,  and  IV,  1875-1878. 

25.  W.   G.   Moenkhaus,  The  development  of  hybrids  between  Fundulus 
heteroclitus  and  Menidia  notata.     Amer.  Journ.  of  Anat.,  Ill,  39-65, 1904. 

26.  E.  G.  Conklin,  Karyokinesis  and  cytokinesis,   etc.,  of  Crepidula  and 
other  Gastropoda.    Journ.  Acad.  Nat.  Sciences,  Philadelphia,  XII,  1902. 

The  organization  and  cell  lineage  of  the  Ascidian  egg.  Journ.  Acad. 
Nat.  Sciences,  XIII,  1-119,  I9°5-  (See  p.  93  ff.) 

27.  F.  R.  Lillie,  Embryology  of  the  Uniomidae.     Journ.  of  Morphology,  X, 
1895. 

Differentiation  without  cleavage  in  the  egg  of  the  annelid  Chsetop- 
terus  pergamentaceous.  Arch,  fur  Entwicklungsmechanik,  XIV,  1902. 

(The  works  of  E.  B.  Wilson,  Arch.  f.  Entwicklungsmechanik,  XVI,  and 
Journal  of  Exp.  Zoology,  I,  may  also  be  compared.  Further,  the  treatise 
of  Yatsu's  Biol.  Bulletin,  VI.) 

28.  E.  Maupas,  Recherches  experimentales  sur  la  multiplication  des  In- 
fusoires  cilies.     Arch.  Zool.  Experim.,  1888. 

'  29.  Calkins  has  caused  several  students  to  carry  on  investigations  on  the 
life  cycle  of  the  Protozoa.  The  newest  one  of  these  is  the  investigation 
of  Miss  J.  E.  Moody,  which  was  published  in  the  Journal  of  Morphology, 
XXIII,  Heft  3  (Sept.,  1912),  349-408.  Miss  Moody  cites  the  earlier 
literature  and  presents  a  good  discussion  of  "depression"  to  the  reader. 

30.  H.  S.  Jennings,  Assortative  mating,  variability,  and  inheritance  of  size 
in  the  conjugation  of  Paramecium.     Journ.  Exp.  Zool.,  XI,  1-134,  1911. 

31.  C.  M.  Child,  A  study  of  senescence  and  rejuvenation  based  on  experi- 
ments with  Planaria  dorotocephala.     Arch,  fur  Entwicklungsmechanik, 
XXXI,  537-6i6,  1911. 

32.  E.   G.   Conklin,   Cell  size  and  nuclear  size.     Journ.  Exp.  Zool.,  XII, 
1-98,  1912. 

Body  size  and  cell  size.     Journ.  of  M  or  ph.,  XXIII,  159-188,  1912. 
\  33.  C.  S.  Minot,  Senescence  and  rejuvenation,     ist  paper.     On  the  weight 
of  guinea-pigs.     Journ.  of  PhysioL,  XII,  97-153. 

The  results  and  further  conclusions,  as  well  as  justification,  may  be 
found  in  "The  Problem  of  Age,  Growth,  and  Death,"  which  appeared 
in  1908. 

34.  C.  A.  Herter,  Popular  Science  Monthly,  LXXIV,  31  (Jan.,  1909). 

35.  M.  Miihlmann,  Das  Altern  und  der  physiologische  Tod.     Samml.  anat.- 
physiol.  Vortrage  (Gaupp  u.  Nagel),  Heft  XI,  Jena,  1910. 

•The  earlier  works  of  the  author  are  cited.  The  criticism  of  Minot 
may  be  found  on  p.  22.  Minot's  criticism  of  Miihlmann  appears  on  p. 
28  of  the  book  "Age,  Growth  and  Death." 


122  NOTES 

36.  Alexander  Goette,  Ueber  den  Ursprung  desTodes,  1883. 

37.  von  Hansemann,  Deszendenz  und  Pathologic,  Berlin,  1909. 

38.  H.  H.  Donaldson,   The   extensive  work  on   the   embryonic  growth  of 
the  white  rat  has  not  yet  appeared.     Donaldson's  comparison  of  the 
white  rat  with  man  in  respect  to  growth  has  particular  interest.     Boas 
Memorial  Volume,  1906. 

39.  C.  S.  Minot,  Human  Embryology,  New  York,  1892. 

40.  Thomas  H.  Morgan  has  treated  the  subject  of  the  relation  of  egg-size, 
etc.,  to  the  determination  of  sex  in  an  excellent  manner  in  his  book, 
"Experimental  Zoology,"  New  York,  1907,  p.  391-426. 

41.  Kuschkakewitz,  Richard  Hertwigs  Festschrift,   1910.     The  criticism  of 
T.  H.  Morgan  should  be  noticed  concerning  the  experiments  of  R.  Hert- 
wig  and  Kuschkakewitz. 

42.  Helen  D.  King,  Studies  on  sex-determination  in  amphibians. 

1907.     Biological  Bulletin,  XIII. 

1909.  Biological  Bulletin,  XVI. 

1910.  Biological  Bulletin,  XVIII, 

1911.  Biological  Bulletin,  XX. 

1912.  V.  The  effects  of  changing  the  water  content  of  the  egg,  etc. 
Journ.  Exp.  ZooL,  XII,  319-336. 

43.  C.  E.  McClung,  The  spermatocyte  divisions  of  the  Acrididae.     Kansas 
University  Quarterly,  January,  1900,  73-100.     Pis.  XV-XVII. 

The  accessory  chromosome-sex  determinant?     Biological  Bulletin,  III, 
43-84,  1902. 

44.  E.  B.  Wilson  has  given  us  two  excellent  summaries  on  the  results  of  in- 
vestigations  on   accessory  chromosomes  in  the  year  1909,  in  Science, 
XXIX,  53-70,  and  in  the  year  1911,  in  the  Arch,  fiir  Mikrosk.  Anat., 
Vol.  77,   249-271.     His  own  papers  have  appeared  chiefly  under  the 
title  "Studies  on  Chromosomes." 

1.  1905.  Journal  of  Experimental  Zoology,  II,  Heft  3. 

2.  1905.  Journal  of  Experimental  Zoology,  Bd.  II,    Heft  4. 

3.  1906.  Journal  of  Experimental  Zoology,  Bd.  III. 

4.  1909.  Journal  of  Experimental  Zoology,  Bd.  VI,  Heft  2. 

5.  1909.  Journal  of  Experimental  Zoology,  Bd.  VI,  Heft  2. 

6.  1910.  Journal  of  Experimental  Zoology,  Bd.  IX. 

7.  1911.  Journal  of  Morphology,  XXII,  71. 

45.  The  following  researches  on  the  spermatogenesis  of  Anasa  are  known  to 
the  author. 

Fr.  C.  Paulmier,  1899,  Journal  of  Morphology,  XV,  Suppl. 
E.  B.  Wilson,  1905,  Journal  Exp.  Zoology,  II 
E.  B.  Wilson,  1907,  Science,  XXV,  631. 


NOTES  123 

Foote  and  Strobell,  1907,  Biological  Bulletin,  XII. 
Foote  and  Strobell,  1907,  American  Journ.  Anat.,  VII,  279-316. 
Lefevre  and  McGill,  1908,  American  Journ.  Anat.,  VII,  469-485. 
C.  V.  Morril,  1909,  Biological  Bulletin,  XIX. 

C.  E.  McClung  and  Edith  Pinney,  An  examination  of  the  chromo- 
somes of  Anasa  tristis.  The  Kansas  University  Science  Bulletin,  V,  No. 
20,  349-380. 

To  those  who  would  like  to  acquaint  themselves  further  with  this  sub- 
ject, this  excellent  article  is  especially  recommended.  It  is  distinguished 
by  its  concise,  clear  and  exhaustive  pVesentaticn. 

46.  Miss  N.  M.  Stevens  studied  chromosomes  in  many  insects  with  great 
skill  and  success. 

1908.  Diptera.     Journal  Exp.  Zoology,  V,  359. 

1908.  Diabrotica.     Journ.  Exp.  Zoology,  V,  453. 

1909.  Coleoptera.     Journ.  Exp.  Zoology,  VI,  101. 
1909.  Aphidae.     Journ.  Exp.  Zoology,  VI,  115. 

Compare  also  Biol.  Bull.,  XVIII,  73-75,  1910. 

47.  Miss  N.  M.  Stevens.     Preliminary  note  on  heterochromosomes    in    the 
guinea-pig.     Biol.  Bulletin,  XX,  121-122,  1912. 

Heterochromosomes  in  the  guinea-pig.     Biol.  Bulletin,  XXI,  155-167. 

48.  Michael  F.  Guyer,The  spermatogenesis  of  the  domestic  guinea  (Numidia 
meleagris  dom.).     Anat.  Am.,  XXXIV,  502-513,  1909. 

Accessory  chromosomes  in  man.     Biol.  Bulletin,  XIX,  219-234. 

49.  T.  H.  Morgan,  A  biological  and  cytological  study  of  sex  determination 
in  Phylloxerans  and  Aphids.     Journ.  Exp.  Zoology,  VII,  239-352,  1909. 
(Also  several  preliminary  communications.) 

50.  H.  S.  Pratt,  Science,  1912.     The  author  states  the  following  estimations 
of  the  number  of  known  species  of  animals: 

Linne 1758  4,236 

Agassiz  and  Bronn 1859  129,530 

Ludwig  (Leuiiis) 1886  272,220 

Pratt 1911  522,400 

51.  Helmholz  is  not  the  author  of  the  hypothesis  that  meteorites  brought 
life  to  our  earth.     As  early  as  1871  it  was  introduced  by  Sir  William 
Thompson  in  his  Presidential  Address  before  the  British  Association.     So 
also  the  hypothesis  of  Arrhenius,  which,  according  to  Schafer,  was  orig- 
inated by  Cohn  (1872)  and  Richter  (1875). 

52.  E.  Pfliiger,  Ueber  die  physiologische  Verbrennung  in  den  lebendigen 
Organismen.    Pflugers  Arch,  gesamt.  PhysioL,  X,  251-367,  1875.     (See 

P-  339  #•) 

53.  T.  H.  Morgan  utilized  Drosophila  for  many  experiments  on  heredity. 


124  NOTES 

The  larvae  live  on  fruits  and  compkte~Eheir  metamorphosis  in  about 
three  weeks.  Thus  one  can  cultivate  many  generations  of  these  small 
flies  very  easily  and  quickly.  The  principal  investigation  on  the  eyes 
will  appear  soon  in  the  Journal  of  the  Academy  of  Sciences,  Philadelphia. 
The  experiments,  however,  are  still  being  carried  on.  Morgan  has 
published  other  researches  on  Drosophila.  See  Science,  XXXII,  p. 
120;  XXXII,  p.  496;  XXXIII,  p.  534;  XXXIV5  p.  384.  Also,  Journal 
Exp.  ZooL,  XI,  365-411,  1911.  (Heredity  in  eye  color,  with  figures.) 

54.  C.  R.  Stockard,     The  development  of  artificially  produced  Cyclopean 
fish — "The  magnesium  embryo."    Journ.  Exp.  ZooL,  VI,  285-337,  1908. 

55.  A.  P.  Matthews,  Some  ways  of  causing  mitosis  in  unfertilized  Arbacia 
eggs.     Amer.  Journ.  Physiol.,  1900,  VI,  343-347. 

56.  J.  Loeb,  On  the  nature  of  the  process  of  fertilization  and  the  artificial 
production  of  normal  larvae  (Plutei)  from  the  unfertilized  egg  of  the  sea- 
urchin.     Amer.  Journ.  Physiol.,  1900,  III,  135-138. 

On  the  artificial  production  of  larvae  from  the  unfertilized  eggs  of  the 
sea-urchin  (Arbacia).  Amer.  Journ.  Physiol.,  1900,  III,  434-471. 
(Preliminary  communication,  Ibid.,  135-138.) 

Experiments  on  artificial  parthenogenesis  in  annelids  and  the  nature 
of  the  process  of  fertilization.  Amer.  Journ.  Physiol.,  1901,  IV,  423-459. 
(Compare  also  Ibid.,  178-184). 

57.  E.  B.  Meigs,  Zeitschr.  f.  allgem.    Physiologie,  1908,  VIII,  81.     Amer. 
Journ.  Physiol.,  1908,  XXII,  477.     Amer.  Journ.  Physiol.,  1912,  XXIX, 

317- 

58.  C.  F.  Hodge,  Changes  in  ganglion  cells  from  birth  to  senile  death.     Journ. 
of  Physiol.,  XVII,  129-134. 

59.  R.  R.  Bensley,  Studies  on  the  pancreas  of  the  guinea-pig.     Amer.     Journ. 
of  Anat.,  XII,  297-388,  1911. 

60.  Charles  S.  Minot,  The  problem  of  consciousness  in  its  biological  aspects. 
Presidential  address  before  the  American  Association  for  the  Advance- 
ment of  Science. 

Science,  XVI,  1-12,  1902.  German  translation  in  the  volume,  "Die 
Methode  der  Wissenschaft,"  published  by  Gustav  Fischer,  1913. 


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